Development of human cerebellar nuclei. Morphometric study

The morphometric development of the human cerebellar nuclei was examined in 9 fetuses (16-40 weeks of gestation; WG), an infant (2 months old) and 2 adults (16 and 63 years old). With the morphological observation of serial sections of the brain containing the cerebellar nuclei, the authors measured sections to get several morphometric parameters: the volume of nuclear column and number, packing density and cell body area of neurons. Each nucleus (dentate, emboliform, globose and fastigial nucleus) was recognized even at 16 WG. Nerve cells containing Nissl bodies were observed in all nuclei after 23 WG. Degenerative changes were detected in some neurons for every nucleus at 21 and 23 WG. Three stages were observed in the developmental course of nuclear volume and neuronal packing density: the primary or undifferentiated stage at 16 WG, the secondary stage with variability at 21-32 WG and the tertiary stage with monotonous increase (nuclear volume) or gradual decrease (neuronal packing density) after 35 WG. No significant correlation between neuronal number and gestational age was noticed for every nucleus. The analysis of cell body area (neuronal size) demonstrated that the dentate neurons developed after the intermediate or fastigial neurons. It is concluded that there is a critical period between slightly before 20 WG and slightly after 30 WG, matched with the secondary stage in the development of the cerebellar nuclei.     

Bilateral otolith contribution to spatial coding in the vestibular system

Recent work on the coding of spatial information in central otolith neurons has significantly advanced our knowledge of signal transformation from head-fixed otolith coordinates to space-centered coordinates during motion. In this review, emphasis is placed on the neural mechanisms by which signals generated at the bilateral labyrinths are recognized as gravity-dependent spatial information and in turn as substrate for otolithic reflexes. We first focus on the spatiotemporal neuronal response patterns (i.e. one- and two-dimensional neurons) to pure otolith stimulation, as assessed by single unit recording from the vestibular nucleus in labyrinth-intact animals. These spatiotemporal features are also analyzed in association with other electrophysiological properties to evaluate their role in the central construction of a spatial frame of reference in the otolith system. Data derived from animals with elimination of inputs from one labyrinth then provide evidence that during vestibular stimulation signals arising from a single utricle are operative at the level of both the ipsilateral and contralateral vestibular nuclei. Hemilabyrinthectomy also revealed neural asymmetries in spontaneous activity, response dynamics and spatial coding behavior between neuronal subpopulations on the two sides and as a result suggested a segregation of otolith signals reaching the ipsilateral and contralateral vestibular nuclei. Recent studies have confirmed and extended previous observations that the recovery of resting activity within the vestibular nuclear complex during vestibular compensation is related to changes in both intrinsic membrane properties and capacities to respond to extracellular factors. The bilateral imbalance provides the basis for deranged spatial coding and motor deficits accompanying hemilabyrinthectomy. Taken together, these experimental findings indicate that in the normal state converging inputs from bilateral vestibular labyrinths are essential to spatiotemporal signal transformation at the central otolith neurons during low-frequency head movements.     

Quantitative comparison of the hominoid thalamus. I. Specific sensory relay nuclei.

Studies to date have indicated few differences in sensory perception among hominoids. Sensory relay nuclei in the dorsal thalamus--portions of the medial and lateral geniculate bodies (MGBp, LGBd) and the ventrobasal complex (VB)--in two gibbons, one gorilla, one chimpanzee and three humans were examined for anatomical similarity by measuring and estimating the nuclear volumes, neuronal densities, numbers of neurons per nucleus, and volumes of neuronal perikarya. The absolute volumes of these nuclei were larger in the larger brains; however, with the volume of the dorsal thalamus as a standard, these sensory relay nuclei showed negative allometry. The gibbons had about half as many neurons as did the other hominoids. Although the human VB had slightly more neurons, the numbers of neurons in LGBd and MGBp did not significantly differ between the great apes and humans. The volumetric distribution of the neuronal perikarya were similar among these hominoids. Other thalamic nuclei had much more diverse numbers of neurons and relative frequencies of their neuronal perikarya. The sensory relay nuclei appear to be a group of conservative nuclei in the forebrain. These results suggest that as a neurological base for complex behaviors evolved in hominids, not all parts of the brain changed equally.     

Distribution of Fos-Like Immunoreactivity,Catecholaminergic and Serotoninergic Neurons Activated by the Laryngeal Chemoreflex in the Medulla Oblongata of Rats

The laryngeal chemoreflex (LCR) induces apnea, glottis closure, bradycardia and hypertension in young and maturing mammals. We examined the distribution of medullary nuclei that are activated by the LCR and used immunofluorescent detection of Fos protein as a cellular marker for neuronal activation to establish that the medullary catecholaminergic and serotoninergic neurons participate in the modulation of the LCR. The LCR was elicited by the infusion of KCl-HCl solution into the laryngeal lumen of adult rats in the experimental group, whereas the control group received the same surgery but no infusion. In comparison, the number of regions of Fos-like immunoreactivity (FLI) that were activated by the LCR significantly increased in the nucleus of the solitary tract (NTS), the vestibular nuclear complex (VNC), the loose formation of the nucleus ambiguus (AmbL), the rostral ventral respiratory group (RVRG), the ventrolateral reticular complex (VLR), the pre-Bötzinger complex (PrBöt), the Bötzinger complex (Böt), the spinal trigeminal nucleus (SP5), and the raphe obscurus nucleus (ROb) bilaterally from the medulla oblongata. Furthermore, 12.71% of neurons with FLI in the dorsolateral part of the nucleus of the solitary tract (SolDL) showed tyrosine hydroxylase-immunoreactivity (TH-ir, catecholaminergic), and 70.87% of neurons with FLI in the ROb were serotoninergic. Our data demonstrated the distribution of medullary nuclei that were activated by the LCR, and further demonstrated that catecholaminergic neurons of the SolDL and serotoninergic neurons of the ROb were activated by the LCR, indicating the potential central pathway of the LCR.     

Chromatin changes in frog neurons after eighth nerve transection

Fourteen days after unilateral eighth nerve transection in the frog, Purkinje neurons of the lobus vestibulolateralis and corpus of the cerebellum and medium-sized neurons of the vestibular nuclear complex showed changes in metabolic activity. In the ipsilateral parts, and to a lesser extent in the contralateral parts, of operated frogs, the Feulgen-DNA values were higher and the nuclear areas larger, associated with decondensation of chromatin. The cytoplasmic basophilia was also less. These changes could be due to anabolic responses of the neuronal populations during regeneration. The anabolic reaction of the corpus cerebelli and contralateral vestibular nuclear complex is only partially non-specific and ascribable to the surgical trauma (comparison between sham-operated and unoperated frogs). The results indicate clear patterns of connection between the ipsilateral and contralateral parts and between the cerebellar and vestibular nuclear complex neurons.     

Vestibular nuclei in the guinea pig: Structural and topical organization

The topological and cytoarchitectonic organization of the vestibular nuclear complex was investigated in guinea pigs. The cellular composition of the superior, lateral, medial, and inferior vestibular nuclei was described by using neutral red stained preparations together with that of neuronal groups (I, F, Y, X, and Z) indirectly associated with the vestibular nuclear complex. Boundaries and stereotaxic coordinates of vestibular complex structures were defined by glycerol-processed frontal serial brain slices measuring 50 µm thick.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 5, pp. 650–657, September–October, 1990.     

Immunohistochemical mapping of adrenomedullin in the human medulla oblongata

We studied by immunocytochemistry the expression of adrenomedullin (AM) in the human medulla oblongata, sampled from 13 adult subjects (mean age: 38 years), whose medical history was negative for neurological and neurovascular pathologies. Immunoreactive neurons were found in the medulla oblongata with statistically significant differences among the various nuclei (one-way ANOVA, P < 0.001). The hypoglossal nucleus showed higher AM expression than that of the spinal tract of the trigeminal nerve (P < 0.05), solitary tract nucleus (P < 0.05), nucleus intercalatus (P < 0.05), and area postrema (P < 0.05). The arcuate nucleus and inferior olivary nuclear complex showed lower AM expression than the hypoglossal nucleus (P < 0.001), vestibular nuclei (P < 0.01), cuneate and gracile nuclei (P < 0.05), lateral column of the reticular formation (P < 0.05), and nucleus ambiguous (P < 0.05). Furthermore the nuclei were grouped with reference to their function, into somatic sensitive nuclei, somatic motor nuclei, visceral nuclei, reticular formation, and nuclei involved in cerebellar functions. The ANOVA revealed statistically significant differences (P < 0.001) in mean AM scores among the different groups. Nuclei involved in cerebellar function showed the lowest mean AM score (P < 0.05). The difference in AM score between somatic motor nuclei and visceral nuclei was also statistically significant (P < 0.05). Widespread AM immunoreactivity in the nuclei of the medulla oblongata may account for the role of the peptide in neuronal function and regulation of regional blood flow. Differences in the expression of AM in the nuclei studied indicate the different involvement of AM in neurotransmission and neuromodulation.     

Functional organization of the vestibulospinal system in amphibians

In experiments on the preparation of a frog perfused brain, using recording of intracellular potentials the vestibulospinal neurons were identified on the basis of excitatory postsynaptic potentials evoked by the stimulation of the ipsilateral vestibular nerve and antidromic activation from the stimulation of the cervical and lumbar enlargements of the spinal cord. The average conduction velocity determined for axons of C neurons was 10.67 m/s and for L neurons 15.84 m/s. The ratio of C and L neurons over the vestibular nuclear complex was very stimular to each other: 52% C neurons and 48% L neurons. The majority of both types of neurons were localized in the lateral vestibular nucleus (58.6%), to the lesser extent in the descending vestibular nucleus (30.7%) and very little in the medial vestibular nucleus (10.6%). Fast and slow cells were detected among the vestibulospinal neurons. The fast neurons of L cells did not prevail greatly over the slow ones, whereas the slow neurons of C cells prevailed comparatively largely over the fast neurons. Thus, it became possible to reconstruct spatial distribution of the identified vestibulospinal neurons. The results of spatial distribution of C and L vestibulospinal neurons in the frogs failed to conform to definite somatotopy, which is characteristic for mammalian vestibular nuclei. C and L neurons in the frog's vestibular nuclei as a source of vestibulospinal fibres, are scattered separately or more frequently in groups, so that they establish a "patch-like" somatotopy and do not form a distinctly designed fields as in mammals.     

Cytophotometric analysis of T-2 toxin induced alterations in chromatin condensation and neuronal nuclear volume of rat supraoptic-magnocellular neurons

Quantitative cytophotometry and ocular filar micrometry were used to monitor T-2 toxin induced alterations in chromatin and neuronal nuclear volume in supraoptic-magnocellular neurons of rat hypo-thalami. Thirty male Sprague-Dawley rats (200-220g) were given a single i.p. injection of T-2 toxin (0.5, 0.75, 1.0 and 1.5 X LD50), a trichothecene mycotoxin; rats were decapitated 8 hours post-dosing. After stoichiometric Feulgen-DNA staining of brain sections, scanning-integrating microdensitometry was used to quantify changes in the susceptibility of chromatin to Feulgen acid hydrolysis. Changes in neuronal nuclear volumes were also determined histometrically. Within the magnocellular neurons of the supraoptic nuclei, significant reductions in F-DNA reactivity were observed in the 0.5, 0.75, and 1.0 X LD50 groups (i.e. 3.7%, 4.4% and 2.5%, respectively); however, rats receiving 1.5 X LD50 T-2 toxin showed no difference in F-DNA reactivity compared to controls. In addition, ocular filar micrometry demonstrated increased neuronal nuclear volumes in all groups receiving T-2 toxin, and following an inverse trend to that seen with F-DNA stainability. Additional observations included pronounced polydipsia, polyphagia and horripilation in the experimental groups, independent of the dosages employed; these changes were evident within 1 hour post-injection. It is postulated that the T-2 toxin induced reduction in the susceptibility of chromatin to Feulgen acid hydrolysis and concomitant increases in neuronal nuclear volumes represent an early indication of impaired metabolic activity. Since these neurons are important sites of vasopressin (antidiuretic hormone) synthesis, these data suggest an impaired osmoregulatory ability. The pronounced polydipsia which occurred shortly after intoxication is further evidence of this impairment. Although these findings do not provide insight relating to the mechanism of osmoregulatory disruption, it is evident that an impaired ability to osmoregulate is among the earliest indications of acute T-2 toxin mycotoxicosis.     

Lifelong Expression of Apolipoprotein D in the Human Brainstem: Correlation with Reduced Age-Related Neurodegeneration

The lipocalin apolipoprotein D (Apo D) is upregulated in peripheral nerves following injury and in regions of the central nervous system, such as the cerebral cortex, hippocampus, and cerebellum, during aging and progression of certain neurological diseases. In contrast, few studies have examined Apo D expression in the brainstem, a region necessary for survival and generally less prone to age-related degeneration. We measured Apo D expression in whole human brainstem lysates by slot-blot and at higher spatial resolution by quantitative immunohistochemistry in eleven brainstem nuclei (the 4 nuclei of the vestibular nuclear complex, inferior olive, hypoglossal nucleus, oculomotor nucleus, facial motor nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and Roller`s nucleus). In contrast to cortex, hippocampus, and cerebellum, apolipoprotein D was highly expressed in brainstem tissue from subjects (N = 26, 32−96 years of age) with no history of neurological disease, and expression showed little variation with age. Expression was significantly stronger in somatomotor nuclei (hypoglossal, oculomotor, facial) than visceromotor or sensory nuclei. Both neurons and glia expressed Apo D, particularly neurons with larger somata and glia in the periphery of these brainstem centers. Immunostaining was strongest in the neuronal perinuclear region and absent in the nucleus. We propose that strong brainstem expression of Apo D throughout adult life contributes to resistance against neurodegenerative disease and age-related degeneration, possibly by preventing oxidative stress and ensuing lipid peroxidation.     

Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex

Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm(3) and mean cell numbers (x10(6)) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals' age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions.     

A volumetric comparison of the vestibular nuclei in primates

The volumes of each of the four vestibular nuclei, superior, lateral, medial and descending, were measured in 80 brains from 2 species of Scandentia, 18 species of prosimians, and 26 species of anthropoids. Size indices were calculated by comparing species-specific points to the nucleus volume-body weight allometry in prosimians, where the average prosimian was set at 1.00. The indices range from 1.78 in Saimiri to 0.48 in Gorilla, and the distributions by families overlap partially or completely. The observed trend in size indices is independent of changes in the neocortex and the ventral pons; average indices are 1.35 in New World monkeys, 1.20 in Old World monkeys, 0.74 in apes, 0.82 in man. Among prosimians, Galago, Galagoides and Tarsius (leaping locomotion) show significantly higher indices than Nycticebus, Loris and Perodicticus (slow movement without leaping). The lateral vestibular nuclear indices in Pongidae and man are extremely low, about half of those of the average prosimians. Correlation coefficients of size indices between the vestibular nuclei and other motor nuclei, such as the cerebellar nuclei, ventral pons and striatum, are analysed. The ratio of the vestibular nuclear volumes to the total brain volumes and the distribution of percentages of each vestibular nuclear volume to the total complex are also obtained.     

Expression of myosin VIIA in the developing chick inner ear neurons

The auditory-vestibular ganglion (AVG) is formed by the division of otic placode-derived neuroblasts, which then differentiate into auditory and vestibular afferent neurons. The developmental mechanisms that regulate neuronal cell fate determination, axonal pathfinding and innervation of otic neurons are poorly understood. The present study characterized the expression of myosin VIIA, along with the neuronal markers, Islet1, NeuroD1 and TuJ1, in the developing avian ear, during Hamburger–Hamilton (HH) stages 16–40. At early stages, when neuroblasts are delaminating from the otic epithelium, myosin VIIA expression was not observed. Myosin VIIA was initially detected in a subset of neurons during the early phase of neuronal differentiation (HH stage 20). As the AVG segregates into the auditory and vestibular portions, myosin VIIA was restricted to a subset of vestibular neurons, but was not present in auditory neurons. Myosin VIIA expression in the vestibular ganglion was maintained through HH stage 33 and was downregulated by stage 36. Myosin VIIA was also observed in the migrating processes of vestibular afferents as they begin to innervate the otic epithelium HH stage 22/23. Notably, afferents targeting hair cells of the cristae were positive for myosin VIIA while afferents targeting the utricular and saccular maculae were negative (HH stage 26–28). Although previous studies have reported that myosin VIIA is restricted to sensory hair cells, our data shows that myosin VIIA is also expressed in neurons of the developing chick ear. Our study suggests a possible role for myosin VIIA in axonal migration/pathfinding and/or innervation of vestibular afferents. In addition, myosin VIIA could be used as an early marker for vestibular neurons during the development of the avian AVG.     

Neuronal nitric oxide synthase immunopositive neurons in cat vestibular complex: a light and electron microscopic study

Nitric oxide is a unique neurotransmitter, which participates in many physiological and pathological processes in the organism. Nevertheless, there are little data about the neuronal nitric oxide synthase immunoreactivity (nNOS-ir) in the vestibular complex of a cat. In this respect, the aims of this study were to: (1) demonstrate nNOS-ir in the neurons and fibers, from all major and accessory vestibular nuclei; (2) describe their light microscopic morphology and distribution; (3) investigate and analyze the ultrastructure of the NOS I-immunopositive neurons, fibers, and synaptic boutons. For demonstration of the nNOS-ir, the peroxidase–antiperoxidase–diaminobenzidin method was applied. Immunopositive for nNOS neurons and fibers were present in all major and accessory vestibular nuclei. On the light microscope level, the immunopositive neurons were different in shape and size. According to the latter, they were divided into four groups—small (with diameter less than 15 μm), medium-sized (with diameter from 15 to 30 μm), large type I (with diameter from 30 to 40 μm), and large type II (with diameter greater than 40 μm). On the electron microscope level, the immunoproduct was observed in neurons, dendrites, and terminal boutons. According to the ultrastructural features, the neurons were divided into three groups—small (with diameter less than 15 μm), medium-sized (with diameter from 15 to 30 μm), and large (with diameter greater than 30 μm). At least two types of nNOS-ir synaptic boutons were easily distinguished. As a conclusion, we hope that this study will contribute to a better understanding of the functioning of the vestibular complex in cat and that some of the data presented could be extrapolated to other mammals, including human.     

Comparative analysis of vestibulospinal neuron sizes in the guinea pig

A comparison was made between dimensions of vestibular neurons labeled with horseradish peroxidase projecting to the spinal cord and cells stained with neutral red not differentiated into vestibulospinal and not forming descending projections. The cells in nondifferentiated areas of descending, medial and lateral vestibular nuclei include neurons of all sizes. In the caudorostral direction of the vestibular complex, the number of small and average neurons decreased and the number of large and gigantic neurons increased. The vestibulospinal populations included cells of average, large and gigantic size, and large and gigantic neurons were dominant. In the caudorostral direction, neurons of various sizes were distributed relatively evenly without forming differentiated groups.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 5, pp. 616–624, September–October, 1991.     

A quantitative comparison of the hominoid thalamus: II. Limbic nuclei anterior principalis and lateralis dorsalis

Structures in the limbic system are commonly thought to be similar in form and function in all mammalian brains. In the study reported here, two thalamic limbic nuclei, N. anterior principles and N. lateralis dorsalis, were compared among a group of extant of extant hominoids. The nuclear volumes, neuronal densities, number of neurons per nucleus, and volumes of neuronal perikarya were measured. Humans have much larger nuclei but the nuclei constitute a similar proportion of the whole thalamus as found in the other hominoids. Whereas the human limbic nuclei were observed to have a decrease in the densities of nerve cells compared with those of the other hominoids, this difference is less than that found in most other thalamic nuclei. Consequently the estimated number of neurons is much higher for humans. The total number of neurons best separates the human limbic nuclei from those of the other hominoids. This preliminary study suggests that during hominid evolution neurons were preferentially added to the limbic nuclei of the thalamus.     

Neurogenic potential of the vestibular nuclei and behavioural recovery time course in the adult cat are governed by the nature of the vestibular damage

Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of clinical relevance in vestibular pathology.     

Neuron loss and addition in developing zebra finch song nuclei are independent of auditory experience during song learning

In zebra finches early auditory experience is critical for normal song development. Young males first listen to and memorize a suitable song model and then use auditory feedback from their own vocalizations to mimic that model. During these two phases of vocal learning, song-related brain regions exhibit large, hormone-induced changes in volume and neuron number. Overlap between these neural changes and auditory-based vocal learning suggests that processing and acquiring auditory input may influence cellular processes that determine neuron number in the song system. We addressed this hypothesis by measuring neuron density, nuclear volume, and neuron number within the song system of normal male zebra finches and males deafened prior to song learning (10 days of age). Measures were obtained at 25, 50, 65, and 120 days of age, and included four song nuclei: the hyperstriatum ventralis pars caudalis or higher vocal center (HVc), Area X, the robust nucleus of the archistriatum (RA), and the lateral magnocellular nucleus of the anterior neostriatum (IMAN). In both HVc and Area X, nuclear volume and neuron number increased markedly with age in both normal and deafened birds. The volume of RA also increased with age and was not affected by early deafening. In IMAN, deafening also did not affect the overall age-related loss of neurons, although at 25 days neuron number was slightly less in deafened than in normal birds. We conclude that while the addition and loss of neurons in the developing song system may provide plasticity essential for song learning, these changes do not reflect learning.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chronic alcoholism on the human hippocampus

The effect of chronic alcoholism on the human hippocampus was studied in 21 patients, divided in 4 groups: Group A under 45 years, group B 46-59 years, group C 60-69, and Group D over 70 years; and compared with age-matched control patients who died without neurological complications. The gyrus dentatus and the ammonic fields CA1 through CA4 were analyzed by counting the number of neurons and the size of the nuclear area. Both parameters were evaluated statistically. The most important findings were a high neuronal loss in alcoholics in the first age group. In addition, the hippocampal neurons failed to display a vicarious reaction, since the nuclei did not show any increase in size despite the intense neuronal loss. Our results point out an early neuronal loss in the hippocampus of alcoholic patients higher than age-matched controls, as well as a lack of reaction to the neuronal insult.