Decreased Resting Functional Connectivity after Traumatic Brain Injury in the Rat

Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.     

Total RNA content and blood flow in rat brain after RNA administration

The changes in blood flow through selected brain structures and the changes in the total RNA content of cells of these structures were examined after a single administration of yeast RNA to 6-month-old male rats. The total content of ribosomal RNA in cells of the limbic system (septum, hippocampus, hypothalamus) increased 48 hrs after the administration of 100 mg i.p. yeast RNA , dropped after 7 days (in hypothalamus), 21 and 30 days (in hippocampus), 30 days (in septum). In cells of the limbic system as a whole there is a higher total RNA content in experimental rats. No changes were observed in the cells of parietal brain cortex. Blood flow increased in limbic structures 21 and 30 days after RNA administration and in septum and in hippocampus also 90 days after application. No changes were observed in parietal brain cortex, bulbi olfactorii, cerebellum and brain stem. Histochemical changes correlated positively with blood flow changes in the limbic system 14, 21, 30 and 90 days after RNA application. The body weight of experimental rats did not differ from that of control animals. The changes in haemodynamic parameters were transient and were demonstrated as fluctuations in heart rate, cardiac output, and peripheral resistance. Blood pressure experienced no changes.     

Estimation of localization and dipole moment of alpha- and theta-rhythm sources by cluster analysis in healthy subjects and schizophrenics

In 12 healthy subjects and 9 schizophrenic patients in the background conditions (with eyes closed) EEG was recorded from 16 standard derivations (10-20 system) during 3 min. The record underwent the spectral analysis detecting alpha- and theta-frequency bands. After the preliminary narrow band filtration for the main frequencies the sources of the spontaneous rhythms were localized. The data on localization for all healthy subjects and patients were summarized. The K-means clustering was used for identification of the sources clusters which were revealed in occipital and parietal lobes and limbic cortex for alpha-rhythm and also in frontal, temporal and parietal regions, limbic cortex and hippocampus for theta-rhythm. In schizophrenic patients in comparison with healthy subjects there was revealed significant increase of the numbers of dipole sources of alpha-rhythm in the clusters localized in limbic cortex and hippocampus. For theta-rhythm there was significant increase of the dipole moment of the sources in the clusters localized in the temporal and frontal cortices and hippocampus in patients in comparison with the norm.     

Effect of swinging on EEG of rats of juvenile age in the wakefulness state

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectr electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of delta-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of alpha- and beta1-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.     

Effect of swinging on EEG of rats of juvenile age in the wakefulness state

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectre electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of δ-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of α-and β₁-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.     

Temporal and regional changes of superoxide dismutase and glutathione peroxidase activities in rats exposed to focal cerebral ischemia

Reactive oxygen species are important cause of tissue injury during cerebral ischemia and reperfusion (I/R). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are intracellular enzymes responsible for endogenous antioxidant defense of tissues affected by I/R. The aim of this study was to examine temporal and regional changes of SOD and GSH-Px activities in animals exposed to transient focal cerebral ischemia. Male Wistar Hannover rats were subjected to the right middle cerebral artery occlusion for 2?h. The animals were sacrificed immediately, 0·5, 1, 2, 3, 6, 24, 48, 72 or 168?h after ischemic procedure. SOD and GSH-Px activities were determined spectrophotometrically in the hippocampus and parietal cortex, both unilaterally and contralaterally to the occlusion. Sham-operated animals were used as the control group. Our results indicated that transient focal cerebral ischemia causes significant changes in SOD activities in the hippocampus and parietal cortex such as in GSH-Px activities in the parietal cortex, unilaterally and contralaterally to the lesion in rats during different reperfusion periods. Statistically significant activation of GSH-Px was registered neither in the right nor in the left hippocampus of ischemic animals. Copyright ? 2012 John Wiley & Sons, Ltd.     

阿尔兹海默病小鼠模型的磁共振影像学分析

目的分析和研究阿尔兹海默病（AD）转基因模型小鼠（APP/PS1）活体脑部影像学特征。方法本研究利用7.0 T高场强磁共振成像（MRI）技术,对1、3、5、7、9和11月龄AD转基因小鼠模型及对照组活体脑组织的微观结构变化进行对比研究。定量分析了脑组织顶叶皮层及海马区的横向弛豫时间（T2）、表观扩散系数（ADC）和各向异性分数（FA）随AD小鼠年龄变化情况。结果从9月龄开始AD转基因小鼠顶叶皮层及海马区可见散点状低信号区,并且随年龄增长逐渐增多;AD转基因小鼠顶叶皮层和海马区的T2磁豫时间在1～9月龄过程中有减小趋势,但与对照组无显著性差异;顶叶皮层及海马区ADC值的计算结果表明,7～11月龄AD转基因小鼠的ADC值明显下降（P≤0.05）;同样APP/PS1小鼠的FA值从5月龄就开始降低（P≤0.05）,并且这种差异一直持续到11月龄。结论高场强MRI能够显示AD病变出现早期小鼠顶叶皮层及海马区FA值的明显改变,揭示FA值对早期痴呆症临床诊断具有一定的参考价值。     

Development of Prolonged Focal Cerebral Edema and Regional Cation Changes Following Experimental Brain Injury in the Rat

The present study examined the formation of regional cerebral edema in adult rats subjected to lateral (parasagittal) experimental fluid-percussion brain injury. Animals receiving fluid-percussion brain injury of moderate severity over the left parietal cortex were assayed for brain water content at 6 h, 24 h, and 2, 3, 5, and 7 days post injury. Regional sodium and potassium concentrations were measured in a separate group of animals at 10 min, 1 h, 6 h, and 24 h following fluid-percussion injury. Injured parietal cortex demonstrated significant edema, beginning at 6 h post injury (p less than 0.05) and persisting up to 5 days post injury. In the hippocampus ipsilateral to the site of cortical injury, significant edema occurred as early as 1 h post injury (p less than 0.05), with resolution of water accumulation beginning at 3 days. Sodium concentrations significantly increased in both injured cortex (1 h post injury, p less than 0.05) and injured hippocampus (10 min post injury, p less than 0.05). Potassium concentrations fell significantly 1 h post injury within the injured cortex (p less than 0.05), whereas significant decreases were not observed until 24 h post injury within the injured hippocampus. Cation alterations persisted throughout the 24-h post injury period. These results demonstrate that regional brain edema and cation deregulation occur in rats subjected to lateral fluid-percussion brain injury and that these changes may persist for a prolonged period after brain injury.     

Reduction of glial glutamate transporters in the parietal cortex and hippocampus of the EL mouse

There is extensive experimental evidence indicating a crucial role for glutamate in epileptogenesis and epileptic activity. The glial glutamate transporters GLT1 and GLAST are proposed to account for the majority of extracellular glutamate re-uptake. In the present study, polyclonal antibodies specific to GLT1 and GLAST were generated and characterized, revealing distribution patterns for the two transporters confirming those previously reported. In situ hybridization and immunoblotting were then used to compare levels of these two transporters in the parietal cortex and hippocampus of unstimulated and stimulated EL mice with DDY control mice. Additionally, HPLC determined tissue glutamate concentrations in the same regions of these animals. These experiments revealed reductions in GLT1 mRNA and protein in the parietal cortex of unstimulated and stimulated EL mice compared with DDY controls, accompanied by an increase in tissue glutamate concentration in the stimulated EL mice group. GLT1 mRNA was also reduced in the CA3 hippocampal subfield of both unstimulated and stimulated EL mice. GLAST protein was reduced in the hippocampus of the stimulated EL mice group, while no changes in GLAST mRNA or protein were detected in the parietal cortex of EL mice when compared with DDY controls. The glial glutamate transporter down-regulation reported here may play a role in seizure initiation, spread and maintenance in the EL mouse.     

Demonstration of reduced levels of zinc in rat brain after treatment with d-amphetamine, but not after treatment with reserpine

Histochemical and atomic absorption spectrophotometric methods were used to study the effects of reserpine and d-amphetamine on the neuronal trace metal distribution in various regions of the central nervous system (hippocampus, parietal cortex, cerebellum). Six hours after single d-amphetamine treatment (15 mg/kg i.p.), the neuronal zinc level was significantly decreased in the hippocampus and in the parietal cortex. The intensity of sulphide silver staining was similarly greatly decreased in all layers of the hippocampus and the parietal cortex. Such a change was not observed when d-amphetamine was administered in a lower dose (5 or 10 mg/kg i.p.). Twenty hours after single reserpine treatment (10 mg/kg i.p.), there were no changes in the tissue levels and distribution of zinc, copper, iron and manganese. In animals treated with reserpine on five consecutive days, in a dose of 10 mg/kg/day i.p., the trace metal distribution twenty hours following the final treatment was essentially the same as in the control. The results strongly suggest that zinc does not play a direct role in vivo in the storage and mobilization processes of the catecholamines. A high dose of d-amphetamine, however, has a non-specific, toxic effect that is not interrelated with the catecholaminergic neuronal function; this effect is manifested in a diminished intensity of sulphide silver staining and in a reduction of the tissue zinc level.     

Electroencephalographic Correlates of Brain States during Verbal Learning: II. Characteristics of EEG Spatial Synchronization

Spatial EEG synchronization was studied using mean EEG coherences in 57 subjects in a resting state with the eyes open, during memorization of verbal bilingual semantic pairs (Latin and Russian), and during retrieval (monitoring) of the learned information. Statistical comparison of the EEG spectral power in the frequency bands θ, α ₁, α₂, β₁, β₂, and γ showed that induction of the states of memorization and retrieval of the verbal information resulted in multiple significant increases in the mean coherence (spatial synchronization) as compared to the state of rest. These increases were significantly higher in the state of retrieval than in the state of memorization. Such changes simultaneously occurred in different frequency bands and over the entire cortex. The highest relative augmentations of coherence with the highest significance estimates were observed in long-distance derivation pairs involving the temporal areas or combining the anterofrontal and frontal derivations with the parietal and occipital ones. The results are discussed in combination with data obtained in the same study for changes in EEG local synchronization and reported earlier. The intense rearrangements of the bioelectrical activity of the cortex may be determined both by the effect of cognitively specific mechanisms of encoding-decoding of information in the memory system and by a cognitively nonspecific modulating system of the brain.     

Cholinergic Deficit Induced by Ethylcholine Aziridinium (AF64A) Transiently Affects Somatostatin and Neuropeptide Y Levels in Rat Brain

The question whether during the process of cholinergic degeneration somatostatin- and/or neuropeptide Y-containing neurons in rat hippocampus and cortex react to the withdrawal of cholinergic function was addressed. After bilateral intracerebroventricular injection of the cholinotoxin ethylcholine aziridinium (AF64A; 1 or 2 nmol/ventricle) in rats, the activity of choline acetyltransferase (ChAT) started to decline in the hippocampus within 24 h. The reduction of ChAT activity reached its maximum within 4 days (34 and 55% after 1 and 2 nmol of AF64A/ventricle, respectively) and persisted during the observation period of 14 days. In the parietal cortex, ChAT activity decreased by 23% 4 days after 2 nmol of AF64A/ventricle. The loss in ChAT activity was accompanied by a transient decline in the levels of somatostatin and a transient increase in the levels of neuropeptide Y in both brain areas. In the hippocampus, the reduction in somatostatin content was most pronounced after 2 days (by 22 and 33% after 1 and 2 nmol of AF64A/ventricle, respectively). Within 14 days, somatostatin levels returned to control values. Neuropeptide Y levels increased slightly by approximately 25% of control values in the hippocampus. The changes described were present in both the dorsal and ventral subfields of the hippocampus. Similar but less pronounced changes in levels of both neuropeptides were observed in the parietal cortex. The present data provide further evidence for a close neuronal interrelationship between cholinergic and somatostatin- and/or neuropeptide Y-containing neurons in rat hippocampus and parietal cortex.     

Localizing Movement-Related Primary Sensorimotor Cortices with Multi-Band EEG Frequency Changes and Functional MRI

Electroencephalographic (EEG) oscillations in multiple frequency bands can be observed during functional activity of the cerebral cortex. An important question is whether activity of focal areas of cortex, such as during finger movements, is tracked by focal oscillatory EEG changes. Although a number of studies have compared EEG changes to functional MRI hemodynamic responses, we can find no previous research that relates the fMRI hemodynamic activity to localization of the multiple EEG frequency changes observed in motor tasks. In the present study, five participants performed similar thumb and finger movement tasks in parallel EEG and functional MRI studies. We examined changes in five frequency bands (from 5–120 Hz) and localized them using 256 dense-array EEG (dEEG) recordings and high-resolution individual head models. These localizations were compared with fMRI localizations in the same participants. Results showed that beta-band (14–30 Hz) desynchronizations (power decreases) were the most robust effects, appearing in all individuals, consistently localized to the hand region of the primary motor cortex, and consistently aligned with fMRI localizations.     

Demonstration of reduced levels of zinc in rat brain after treatment with d-amphetamine,but not after treatment with reserpine

Summary Histochemical and atomic absorption spectrophotometric methods were used to study the effects of reserpine and d-amphetamine on the neuronal trace metal distribution in various regions of the central nervous system (hippocampus, parietal cortex, cerebellum). Six hours after single d-amphetamine treatment (15 mg/kg i.p.), the neuronal zinc level was significantly decreased in the hippocampus and in the parietal cortex. The intensity of sulphide silver staining was similarly greatly decreased in all layers of the hippocampus and the parietal cortex. Such a change was not observed when d-amphetamine was administered in a lower dose (5 or 10 mg/kg i.p.).Twenty hours after single reserpine treatment (10 mg/kg i.p.), there were no changes in the tissue levels and distribution of zinc, copper, iron and manganese. In animals treated with reserpine on five consecutive days, in a dose of 10 mg/kg/day i.p., the trace metal distribution twenty hours following the final treatment was essentially the same as in the control.The results strongly suggest that zinc does not play a direct role in vivo in the storage and mobilization processes of the catecholamines. A high dose of d-amphetamine, however, has a non-specific, toxic effect that is not interrelated with the catecholaminergic neuronal function; this effect is manifested in a diminished intensity of sulphide silver staining and in a reduction of the tissue zinc level.     

Regional effects of ageing on Na+,K(+)-ATPase activity in rat brain and correlation with multiple unit action potentials and lipid peroxidation.

Effects of ageing on Na+,K(+)-ATPase activity in crude synaptosomal fractions from the rat brain parietal cortex, hippocampus, striatum and thalamus has been studied. From 12 months to 24 months, a progressive decline in enzyme activity in the parietal cortex, hippocampus and striatum was found which correlated with increase in lipid peroxidation in the three brain regions. In the thalamus, ageing did not affect the enzyme activity and lipid peroxidation. Age-related decline in multiple unit action potentials was also observed in two brain regions, viz. hippocampus and parietal cortex. Statistical correlations calculated by Pearson's correlation coefficient showed that decline in Na+,K(+)-ATPase activity correlated to decline in multiple unit action potentials. There was rise in lipid peroxidation also and the data indicate that age-related changes in lipid peroxidation and Na+,K(+)-ATPase activity contribute to the deterioration of electrophysiological activity.     

Changes in local cerebral blood flow during increased general arterial pressure in animals]

General blood pressure was increased in normal rabbits and in the animals with experimental renal hypertension by intravenous injection of noradrenaline; local cerebral circulation was recorded in two areas of the cortex the white matter of the large hemispheres by the method of hydrogen clearance and also by EEG. A number of successive changes of the local cerebral circulation was observed; these changes could be unitypical or different by duration and character on different electrodes. The appearance of pathological forms of electrical activity was noted on the EEG.     

Brain amines and neocortical EEG in young and aged rats

1. Frontal and parieto-occipital electroencephalography (EEG) of young (4 months-old) and aged (17 and 22 months-old) Wistar rats were analyzed, both during movement and during waking immobility. 2. The levels of monoamines, serotonin and their metabolites were measured from the frontal cortex, parieto-occipital cortex, hippocampus, brainstem and midbrain. 3. In aged rats, as compared to young rats, the most apparent changes of the quantitative EEG spectrum were the decreased amplitude of alpha (5-10 Hz) and beta (10-20 Hz) frequency bands in the frontal and parieto-occipital cortices during both movement and waking immobility behavior (p less than 0.05). 4. The levels of dopamine (DA), homovanillinic acid (HVA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) or the ratios of 5-HT/5-HIAA and DA/HVA did not differ between young and aged rats in any brain region studied, with the exceptions of brainstem DA and parieto-occipital 5-HIAA, which were elevated in aged rats (p less than 0.05). 5. In the frontal cortex, hippocampus and midbrain, noradrenaline (NA) levels of aged rats were slightly increased as compared to young rats (p less than 0.05). 6. NA levels of the parieto-occipital cortex and brainstem did not change during aging. 7. Furthermore, there were no clear correlations between the decreased amplitude of the quantitative EEG spectrum and monoamine or serotonin concentrations, or the ratios of 5-HT/5-HIAA and DA/HVA in the cerebral cortex of aging Wistar rat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electroencephalographic characteristics of cognitive-specific attention in verbal learning—II: General characteristics of EEG spatial synchronization

Electroencephalograms (EEGs) were recorded in 19 standard derivations in 88 subjects (students) in states of: rest with the eyes open; memorization (learning) of verbal bilingual semantic pairs (Latin and Russian); and recollection (control) of the memorized information. Estimates of EEG coherence in these states were compared using statistical methods for the frequency bands θ, α₁, α₂, β₁, β₂, and γ. The results of this comparison showed that transition from the state of rest to those of memorization and recollection was accompanied by numerous changes in coherence in all the frequency bands. These changes varied in intensity and embrace practically the entire convexital cerebral cortex. Decrease in EEG coherence was predominant during the transition to the memorization state in various frequency bands, whereas during the transition from the rest state to that of recollection, EEG coherence increased in most of the frequency bands except for the band α₂. The reproducibility of this pattern of changes in EEG coherence is confirmed by the results in the subgroups formed by randomly subdividing the subjects into two groups. We think that the observed intense rearrangement of the spatial synchronization of the cortex electrical activity reflects the reorganization of the functional systems of neuronal ensembles to provide efficient memorization and recollection, respectively.     

Effect of NMDA-receptor ligands on neocortical and hippocampal EEG activity of rat brain.

Neocortex and hippocampus play important role in motor activity, neuronal plasticity and learning and memory mechanisms. Electroencephalographic (EEG) activity of neocortex and hippocampus of rat following NMDA-receptor agonist, N-methyl-D-aspartate (NMDA), 0.25-2 nmol in 10 microliters, ICV and noncompetitive NMDA-receptor antagonists, MK 801 (0.025-0.1 mg/kg, ip) and ketamine (10-50 mg/kg, ip) at OH, 1/2H, 4H, 8H and 24H was recorded. The electrodes were implanted stereotaxically in hippocampus and neocortex respectively. NMDA (0.25 and 1 nmol) showed longer lasting decrease in amplitude in hippocampus and in frequency in cortical neurons while 2 nmol produced epileptogenic neurotoxicity. Opposite effect i.e. increase in amplitude in both, hippocampus and neocortex was observed with MK 801 and ketamine and these agents also showed longer lasting influence. Administration of MK 801 (0.05 mg/kg) and ketamine (50 mg/kg) prior to NMDA 2 nmol protected 40% animals from NMDA-induced neurotoxicity and blockade of NMDA-induced long term influence. The EEG effect of NMDA agonist and NMDA-induced neurotoxicity at higher dose and its modification by NMDA-antagonist, MK 801 and ketamine suggest that beside NMDA agonists (NMDA), its antagonists may, also affect long lasting changes in hippocampus and cortex. These antagonists reverse NMDA-mediated long term influence in these brain areas.     

Changes in labeling of soluble and insoluble rat brain proteins using [3H]-tyrosine as precursor during a learning experiment.

The incorporation of intraventricularly injected L-[3H]-tyrosine into proteins from three rat brain regions was studied during the acquisition of a shock-motivated brightness discrimination. Separating the proteins by means of polyacrylamide gel electrophoresis revealed an increased labeling confined to only a few of the resolved slow-moving bands of soluble and, especially insoluble hippocampus proteins. The labeling of visual cortex proteins showed only minute changes, while the auditory cortex proteins exhibited no differences between trained and nontrained animals.