Electrophysiological indices of degree of functional integration between gratified neural tissue and the host brain

Neocortex from 17–18-day rat embryos was transplanted into the barrel-field cortical area in adult rats. Neuronal response to deflecting the vibrissae was tested in the graft 3–8 months afterwards. Nine out of 11 grafts showed a response to sensory stimulation. Irregular and asynchronous discharges predominated in neuronal background firing activity in these grafts. Generalized slow-wave activity had much in common with that occurring on the diametrically opposite site on the intact host brain cortex. Hypersynchronous volleys were detected in neurons of unresponsive grafts. A predominance of waves within the delta range while other rhythms remained only faint, together with epileptiform sharp spikes were seen in generalized activity. Histological treatment of responding grafts revealed close fusion between tissue and host brain. Non-responsive grafts were surronded by a thick glial scar.Institute of Biophysics, Academy of Sciences of the USSR, Pushchino-on-Oka. Institute of Neurobiology and Brain Research, E. German Academy of Sciences, Magdeburg, E. Germany. Translated from Neirofiziologiya, Vol. 19, No. 4, pp. 498–504, July–August, 1987.     

Transplantation of fetal brain tissue. Some possibilities for neurobehavioral toxicology

Fetal brain tissue transplanted to the brain of an adult mammalian host is known to develop within this environment. The grafted tissue also forms connections with the host brain and can produce recovery from behavioral deficits associated with destruction of parts of the host brain. The ability of grafts of fetal brain tissue to both develop in and form electrophysiologically viable connections with brains previously exposed to neurotoxins is discussed in this review. Restoration of neurotoxin-induced behavioral dysfunction by fetal brain grafts is also discussed. Finally, several uses for neural transplantation in neurotoxicological research are suggested. These uses include restoration of behavioral function, identification of the particular structures responsible for observed behavioral deficits, from among several structures damaged by an environmental neurotoxin, and identification of mechanisms underlying neurotoxicity.     

Neuronal responses of the rate somatosensory cortex transplanted into the vibrissae representation field of the neocortex to the electrical stimulation of the recipient brain

Neuronal responses of the rat somatosensory cortex grafted into damaged host barrel field to electrical stimulation of the host brain were investigated extracellularly in rats under light pentobarbital anaesthesia. The following structures of the host brain were stimulated: ventrobasal complex and posterior thalamic nuclei, ipsilateral area of vibrissae representation in the sensorimotor cortex and contralateral barrel field. Reactivity of the grafted neurones was lower, than in the intact barrel field, but the mean latencies of responses were not significantly different. Stimulation of the thalamic nuclei was more effective than that of the cortical areas both in grafted and intact barrel fields. Posttetanic depression after repetitive stimulation was often observed in the grafts, while posttetanic potentiation was more usual for the intact barrel field. The data show the sources of some functional afferent inputs to the grafts which may be responsible for neuronal reactions to somatosensory stimulation of the host animal.     

Afferent and efferent connections of cortical transplants implanted into the damaged sensorimotor area of the cerebral cortex of mature rats

Afferent and efferent connections of the transplant, implanted in the previously damaged sensorimotor area of the mature rat cerebral cortex have been studied by means of axonal transport of horseradish peroxidase. For 5 months after transplantation neural axons of the transplant are capable to reach the caudo-putamen and thalamic structures, while connections with the spinal cord are absent. The afferent connections of the transplant are minimal and belong only to the neighbouring areas of the cortex and the caudo-putamen of the recipient brain. Presence of efferent projections to the striate and thalamic structures demonstrates specificity of the projections formed; this can be a morphological base for restoration of the functions lost after the damage of the sensorimotor area of the cortex in mature animals.     

Axons of Xenopus neural tube respond to reversals of neural tube orientation

Axonal trajectories of the Kolmer-Agduhr (KA) neurons of Xenopus embryos, were observed after anterior-posterior (A-P) inversions of neural tube grafts to determine whether KA axons follow cell-inherent directional cues, cues from their immediate environment, or rostrocaudal signals from the embryo. KA axons form one of the earliest ascending spinal pathways in Xenopus and are visible in the lateral marginal zone of whole mounts processed for GABA immunoreactivity. Grafts were made at trunk levels at stages 22–24, 3–5 h before the first KA neurons were detectable and prior to axonal outgrowth. Embryos were fixed and immunostained 6–36 h later. KA trajectories within and adjacent to reversed grafts were compared to those of nonrotated control grafts and to neural tube lengths comparable in position and in length in unoperated embryos. Most KA axons within rotated grafts followed the graft's orientation. However, others changed direction, taking novel routes including turning to conform to the orientation of the host embryo. Reorientations were most common near the posterior host/graft interface. Some host KA cells also reoriented, always within a few hundred microns of the graft interface. Taken together, these growth patterns show that most KA axons within the grafts grow normally with respect to the original polarity of the graft neural tube and maintain that direction even into tissue of opposite polarity, suggesting that their routes are mainly determined by cell-intrinsic and/or local tissue factors. However, the reorientation of many other axons, particularly near graft seams, implies that KA axons can respond to local fluctuations in directional or segment identity signals generated in both host and graft after this perturbation. © 1996 John Wiley & Sons, Inc.     

A comparison of the take of embryonic amygdala and visual cortex transplants in the rat brain in connection with the possible compensation of functional disorders]

Transplantation of embryonic (E17-18) visual cortex and amygdala was performed into corresponding damaged areas of the adult rat brain. It was shown in Nissl and Golgi preparations (by comparing qualitative and quantitative findings) that 2-6 months after operation the grafts were successful in case of putting them into the corresponding brain areas (cortex to cortex, or amygdala to amygdala). Graft's integration resulted in a selective increase of dendrite length and ramification towards the area of graft-host interface both in amygdala and visual cortex grafts. In case of inadequate graft-host integration the stratification of the grafted visual cortex could be observed. The structural reorganization of grafted neurones is compared with physiological and behavioural findings during the recovery processes in damaged brain.     

Development of mammalian nervous tissue transplanted into the brain and anterior chamber of the eye: problems and prospects

Some theoretical problems arising in connection with nervous tissue grafting in mammals are discussed. The survival of grafts in the brain and anterior eye chamber is provided by a complex of factors, including peculiarities of immunological reaction, blood-brain barrier and certain characteristics of embryonic nervous tissue. Organotypic development of ectopic grafts suggests a significant autonomy of inner genetic programmes in self-organization of brain structures. Development of the graft-host brain nervous connections is, to a great extent, determined by the factors of topographic closeness and the presence of free postsynaptic structures, without prominent specificity of the graft-brain relationships. Complex neurotrophic interactions, mainly provided by the glial cells, are also found between the graft and damaged host brain. A study of electric activity of the grafted neurons has shown a varying degree of dependence of the functional organization of the brain structures on the environmental afferent influences. The grafts can serve as a chronic endogenous source of neurotransmitters and neurohormones, and, possibly, restore interrupted structural connections, thus providing the compensation of some complex brain functions.     

Survival of embryonic amygdala tissue grafted into various parts of the adult rat brain

It was found during the course of histological examination of preparations containing Nissl and Golgi stained neurons that portions of the embryonic amygdala can successfully survive in the intact adult rat brain. A number of parameters were used enabling development of the graft to be assessed objectively: parenchymal integration index, growth potential, cell density, and vascularization index. By comparing qualitative and quantitative findings of our analyses we showed that location within the host brain is one of the principal factors determining success in graft survival. Grafts transplanted into the cortex survived least well, ventricular cavity transplants fared better, and optimum results were observed with tissue grafted onto the subcortical structures. Normal nerve and glial cells were differentiated in grafts which had taken successfully: capillaries grew into the grafted tissue and common neuropil formed between the graft and the host brain. Structural integration between donor tissue and host brain provides a good model for studying both functional interaction and recovery of function impaired by damage to the host amygdala.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 19, No. 5, pp. 606–612, September–October, 1987.     

Morpho-functional effects of kainic acid injection into the cat's pulvinar-lateralis posterior nucleus complex

The histological, electroencephalographic, behavioral changes as well as the changes in the intensity threshold of stimulation necessary to induce contralateral turning were studied in 16 cats, in which kainic acid (KA) was injected locally into the pulvinar-lateralis posterior nucleus complex (P-LP). In 13 cats a stainless-steel tube with two attached electrodes was implanted in P-LP, and electrodes were also implanted in the ipsilateral dorsal hippocampus, the superior colliculus and the caudate nucleus. KA was injected through the tube using a 10 microliters Hamilton syringe. In other 3 cats, KA was injected stereotaxically through the needle of the Hamilton syringe and two electrodes were implanted in these areas after withdrawal of the syringe. The intensity thresholds of stimulation required to induce turning behavior were controlled before and after KA administration in the 13 cats with an implanted tube and only after KA injections in the three cats without a tube; in these instances the current threshold of the contralateral P-LP served as control. The histological results showed a moderate KA damage of the P-LP, with destruction of neuronal soma and gliosis and additional involvement, in all the experiments, of the dorsal hippocampus; however, passage fibers were spared by the lesions. A dose-dependent epileptic effect of KA was seen, which was slight with the 3 micrograms dose and intense with 6 micrograms. The EEG recording showed a prominent and almost simultaneous epileptic involvement of the hippocampus and the P-LP after KA, with less involvement of the other implanted structures. Turning behavior induced by electrical stimulation of the P-LP was suppressed when the electrode tip was located inside the lesioned area. When the electrode tip was placed inside a slight or moderate damaged tissue, a significative increase in current threshold was found, and finally when the tip of the electrode was outside the lesioned area no change in threshold was observed. These findings do not contradict our previous hypothesis of an intrinsic cholinergic mechanism involved in the turning response evoked by P-LP electrical stimulation, although it cannot be excluded that fibers coming presumably from the superior colliculus or pretectum may contribute to the response.     

Comparative characteristics of activity in grafted and intact neocortex in slice preparations

Background single unit activity and mixed single and multiunit responses to electrical stimulation of rat's embryonic cortex grafted into the somatosensory cortex of adult rats were investigated in a slice preparation. The relative number of neurons exhibiting background activity in the grafts was higher than in slices of intact cortex (23 and 6%, respectively), however, the portion of neurons responding to electrical stimulation of areas of neighboring neocortex in the recipient was lower than in intact cortex. The latent periods of population responses in the grafts were consistently longer than in those in intact neocortex (19.4±5 and 5.8±1.1 msec, respectively), although the extreme values coincided. The duration of population responses in the grafts was approximately an order of magnitude longer. The data presented suggests the existence of local connections between the graft and the brain of the recipient and shows weakness of inhibitory processes in the grafts. A functional integration of graft and brain in recipients with craniocerebral trauma was demonstrated.Institute of Biophysics, Academy of Sciences of the USSR, Pushchino, Moscow. Institute of Neurosurgery, Ministry of Public Health of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 3, pp. 273–280, May–June, 1991.     

Intrastriatal Grafts of Fetal Mesencephalic Cell Suspensions in MPP+-Lesioned Rats: A Microdialysis Study In Vivo

The striatum of rats was lesioned by unilateral administration of MPP⁺. Two weeks later, a suspension of fetal mesencephalic cells (FMC), obtained from 14-day rat embryos, was injected into the lesioned striatum. Two weeks after grafting, the success of implantation and recovery of dopamine function were assessed by tyrosine hydroxylase immunocytochemistry (TH) and the measurement of striatal dopamine content. In addition, the extracellular concentrations of dopamine and dopamine metabolites were studied by microdialysis in vivo before and after perfusion of MPP⁺ to induce dopamine release from vesicular stores. TH+ cell bodies were seen in the lesioned grafted striata, indicating that fetal cells survived in these striata. In addition, there was a marked increase in TH-immunoreactivity in the neuronal fibers and terminals in the area surrounding the cell implant, suggesting a compensatory response of the host tissue which may involve fiber sprouting. Grafting induced a recovery in indices of dopamine function, including recovery in dopamine content, and basal and MPP⁺-induced dopamine release. Thus, grafts of FMC may provide a significant recovery of dopamine function in MPP⁺-lesioned striata.     

The dynamics of intracortical interaction during thinking activities

A new method is described of the brain mapping, based on determination of the probability of appearance of isofrequency components in the EEG derivations allowing to evaluate functional interaction of the brain structures in the process of psychic activity. The process of mental construction of visual image from separate elements includes three stages. At the stage of image search the focus of activity is in the occipital cortical area; in the stage of construction it moves to the frontal cortical areas; completion of the task and verbalization of the image are accompanied by joining of the cortical connections in common system. Alongside with the main focus of activity secondary focuses in the temporal cortex are also revealed during the search of the visual image. The topography of interaction at the frequencies of alpha-range in mainly determined by the stage of image construction. In case of prevalence of the image and abstract thinking shift is marked of the activity focuses at the frequencies of theta-range respectively to the right and left hemispheres.     

Intercentral relations of the electrical processes of the rabbit brain with a polarization dominant

The dynamics of changes in intercentral relations of electrical activity of the sensorimotor and premotor zones of both hemispheres and the ventroposterolateral (VPL) nucleus of the left and right thalamus at formation of motor dominant under the action of the DC anode in the rabbit sensorimotor cortex was studied by the method of spectral-correlation analysis. It is shown that in the much less than dominant much greater than motor analyzer (the sensorimotor cortex and VPL) highly coherent connections of electrical processes are formed in the delta-range with conjugated lowering of biopotential connections between the structures of the motor analyzer of the much less than nondominant much greater than part of the brain. At the same time differently directed connections of electrical processes are formed between the structures of the motor analyzer, and between the premotor cortex and focus area. Thus, during formation of the much less than polarization much greater than dominant, a new structure of the intercentral relations of electrical processes is established not only in the much less than dominant much greater than but also in the other half of the brain.     

Visual thalamic afferents to area 29 of the rat limbic cortex

Afferent connections of the retrosplenial area of the rat limbic cortex were investigated by the retrograde horseradish peroxidase axon transport method. After injection of horseradish peroxidase (HRP) into area 29 of the cortex, HRP-labeled cells were found in the dorsal part of the lateral geniculate body and the posterolateral, pretectal, and anterior dorsal thalamic nuclei. Connections were found between cortical area 29 and visual projection areas (areas 17 and 18a) and with area 29 on the contralateral side of the brain. The results are evidence that all the principal visual structures of the thalamus and the visual cortical projection area form direct projections to the retrosplenial cortex.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 135–139, March–April, 1982.     

Evaluation of neuronal damage following hypoxic-ischaemic brain injury in acute and early chronic periods in neonatal rats

This study was undertaken to investigate the effects of neonatal cerebral hypoxic-ischaemic brain injury (HIBI) in acute and early chronic phases in the rat. HIBI was induced in 7-day-old rat pups by ligation of the right common carotid and then the pups were exposed to 1 h of hypoxia in 8% oxygen. They were divided into two groups: 1-day (acute phase, in the first 24 h) and 5-day (early chronic phase, 120 h). Neuropathological evaluation was performed using the hippocampus, cerebral cortex and basal ganglia on the coronal plane. The following values were obtained: (i) the ratio of the infarcted area; (ii) hemispheric atrophy/asymmetry; (iii) patchy lesions confined to the thalamus, caudate and putamen; (iv) the ratio of damaged neurons to all neurons; and (v) the percentage of apoptotic neurons relative to the total neurons in all brain areas. HIBI-induced global cerebral damage and cellular damage findings did not significantly differ between the two groups. However, they showed a tendency to recover/deteriorate in both acute and early chronic phases. The ratio of ipsi- and contra-lateral hemisphere infarct areas (20.7 and 15.7% vs. 40.1 and 26.7%, respectively), basal ganglia patchy lesion ratio (27.5 vs. 36.7%) and hemispheric atrophy/asymmetry (92.4 vs. 84.7%) were found to be lower in the rat pups in the chronic phase than those in the acute phase. In contrast, increases in the ratio of damaged neurons (16.7 vs. 13.3% in the cerebral and dorsal hippocampus, respectively) and in the ratio of apoptotic neurons (ipsi-lateral: 18 vs. 6%; contra lateral hemispheres: 3.5 vs. 1.7%, respectively) were recorded. It is concluded that cellular damage tends to deteriorate (damaged and apoptotic neurons) while global damage (cerebral infarct and patchy damage) improves with the progression of HIBI. However, further studies are needed in order to elucidate this process.     

Effect of transplantation of embryonic neural tissue on the dynamics of brain edema following experimental craniocerebral trauma

The effect of transplantation of embryonic neural tissue (ENT) on the dynamics of brain edema following heavy craniocerebral trauma (CCT) made to the left parietotemporal area was studied in rats. The brain tissue impedance was measured in the damaged and contralateral hemispheres 1 to 30 days after the trauma in the animals of three groups: (i) without any procedures after the CCT, (ii) with surgical treatment of the damaged brain area, and (iii) with transplantation of 1–2 mm³ sensorimotor cortex fragments from 18-day-old rats grafted into the cavity created by this treatment. At the first day after CCT, the impedance in the damaged hemisphere decreased by 30–37%, while the impedance in the contralateral hemisphere decreased approximately by 20%, compared with the control, which was evidence of the development of intensive generalized edema. In the group of animals with the ENT transplantation, the edema involuted noticeably faster than in the other two groups: the mean impedance value reached 97.9% of the control value (before the damage) already by the 7th post-traumatic day. Complete recovery of the impedance by the 30th day was observed only in the animals with transplantation. The adequacy of an impedancemetric technique for investigation of the dynamics of water-electrolyte re-distribution in the brain tissue, and the mechanisms underlying corrective effect of ENT transplantation on the edema dynamics in the post-traumatic period are discussed.     

Functional recovery after olfactory bulbectomy in rats: effect of embryonal brain grafts

Regeneration of olfactory receptor neurones after bulbectomy can lead to formation of extrabulbar synapses, the functional significance of which remains controversial. Adult hooded rats (n = 27) were bilaterally bulbectomized under pentobarbital anaesthesia. Small pieces of brain tissues (1-2 mm3; OB: olfactory bulb; St: corpus striatum) were obtained from embryos of the same strain and placed into the bulbectomy-produced cavity in contact with the exposed brain surface. Smell was tested at 2- to 3-week intervals from 7 weeks to 7 months after the operation. The latency to find hidden food gradually improved and attained the intact control level in bulbectomized rats without grafts, but remained poor in the OB and St transplanted groups. Seven to ten months after transplantation, spontaneous unit activity and unit reactions to amyl acetate vapours were examined with a carbon fibre microelectrode. Unit responses in the transplants resembled those in the normal OB, but were less pronounced. Morphological examination of the transplant and of its connections with the olfactory receptor neurones and with the host brain suggested that functional recovery was mediated by the connections of the olfactory axons with the remnants of the OB, with the anterior olfactory nucleus and/or with the frontal cortex. The adverse effect of OB and St transplants was probably due to their poor connectivity with the host brain which prevented the regenerating olfactory axons from reaching higher olfactory centres.     

Structural Transformations of the Associative Cortex As the Morphological Base of the Development of Human Cognitive Functions from Birth to 20 Years of Age

The microstructure of the temporo-parieto-occipital subregion and the frontal area of the brain from birth to 20 years of age was studied using computer morphometry. These brain zones are involved in the higher integrative mechanisms of cognitive functioning in children, adolescents and young adults. Structural transformations of the cortex represent a stage-by-stage process. Each stage in the frontal and occipital associative zones has specific temporal limits and is characterized by the quantitative and qualitative specificity of the morphological changes at each of the system levels considered: neuronal, modular, and stratification. The structural modifications from birth to early adulthood are primarily associated with the final development of micro and macroassembles and their structural components, primarily, neurons of various types. The growth and differentiation of neurons involves heterochrony with respect to the terms and developmental rates in the frontal and occipital associative cortex. The terms of the most active synchronous postnatal structural modifications, occurring during the first year of life, during the years 2–3, 6–7, 9–10, and 13–14 were analyzed. It was shown, that local specialization of cellular ensembles at various levels is a consequence of the functional specialization of microensembles, involved in cortical information processing, including cognitive activity and other higher psychophysiological functions of the human brain.     

Disorders of the spatiotemporal organization of the brain’s bioelectrical activity in patients with different depressions of consciousness after severe head injury

Specific changes in the bioelectrical activity of the brain have been found in 27 patients with different levels of posttraumatic consciousness depression (stupor, spoor-coma I, coma II) by the methods of cross correlation, and coherence and factor EEG analysis. The changes in activity of the morphofunctional systems of intracerebral integrations were expressed partly in a decrease in the nonspecific activating effects from brainstem structures, which was reflected in an increase in the slow wave activity along with a considerable decrease in the level of EEG coherence in the α and β ranges. The observed depression of the system’s organization of the interrelations of the bioelectrical brain activity in the frontal and occipital regions of both hemispheres could be due to a decreased activity of the associative systems of intercortical and thalamocortical integration. The results suggest a certain facilitation of the activity of the system providing direct interhemispheric connections through the corpus calossum and other commissural tracts of the telencephalon as a consequence of the depression of the mesodiencephalon structures (which normally largely contribute to the synergistic interhemispheric interaction via synchronous ascending effects on the cortex of both hemispheres). This results in steady, reciprocal, and almost antiphase relations of slow wave activity in symmetrical areas of the hemispheres.     

Recognition of emotions by facial and verbal samples in healthy humans and patients with local brain pathology

The efficiency of emotion recognition by verbal and facial samples was tested in 81 persons (25 healthy subjects and 56 patients with focal pathology of premotor and temporal areas of brain hemispheres). The involvement of some cortical structures in the recognition of the basic emotional states (joy, anger, grief, and fear) and the neutral state was compared. It was shown that the damage to both right and left hemispheres impaired the recognition of emotional states by not only facial but also verbal samples. Damage to the right premotor area and to the left temporal area impaired the efficiency of the emotion recognition by both kinds of samples to the highest degree.