Aspects of synaptic reorganization in the cat sensorimotor cortex after lesion of the symmetrically contralateral hemisphere

During the course of acute experiments, response in cortico-spinal neurons (CSN) to stimulating the ipsilateral ventral thalamic nucleus was investigated by extracellular recording techniques in intact adult cats and others with lesioning inflicted on the contralateral sensorimotor cortex 6–18 months previously. An accelerated stage of growth was noted in monosynaptic IPSP and CSN with slow-conducting axons in animals with surgically-induced lesion, suggesting reorganization of synaptic contacts within the CSN somatodendritic membrane. The collision test was applied to make a complete examination of arborization and of other aspects of CSN axons, as well as the presence of collaterals running to the ventrolateral thalamic nucleus and helping to form the ipsilateral pyramidal tract. The significance is discussed of plastic synaptic rearrangement in the ipsilateral thalamo-cortical reverberating system for formation of the efferent spike train during partial interhemisphere cortical deafferentation.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 22, No. 5, pp. 612–621, September–October, 1990.     

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.     

Suloctidil increases the rat brain cortex microvascular regeneration after a lesion

A "cavity" lesion made by aspiration in the rat occipital cortex induces a parenchymal and a vascular reaction in its vicinity. The first was mainly characterized by cellular necrosis and gliosis, the second by an increase of the vascular network. In vehicle treated rats, a 50% significant increase of the vascular network was observed around the cavity 4 days after the lesion, in comparison to the uninjured contralateral cortex. The effects of a vasoactive substance, suloctidil, on the vascular reaction was studied in the brain cortex. A single oral dose of suloctidil (30 mg/kg; 2 hours before the sacrifice) gave the same effect as the vehicle group. After 8 days of suloctidil oral administration (30 mg/kg; twice daily: 4 days before lesion and 4 days after) a significant increase (123%) of the vascular network was observed around the cavity. The hypothetical ways by which a chronic treatment of suloctidil induces this increase of the neovascularization observed after cortical lesion are discussed.     

Restructuring of the topical organization of the rat motor cortex after damage to the opposite hemisphere

Topical organization of the motor cortex was compared in outbred rats by the method of intracortical microstimulation in the norm and in different periods after unilateral partial decortication of the motor projection (MP) of the hind-leg. Stable state of the MPs of the fore- and hind-limbs was in the norm, and within their bounds there was an individual variability of MP zones of separate joints. After the operation, the reconstruction of the motor cortex organization in the opposite hemisphered appeared in later periods, in 5-7 months. Expansion was observed of the boundaries of the excitable area in caudal direction and reduction of the part of responses of the limbs distal muscles as compared to proximal ones and of the body muscles. 8-16 months after the operation, the reactions of axial muscles, including the ipsi- and bilateral ones, became more expressed.     

Increased expression of BAG-1 in rat brain cortex after traumatic brain injury

BAG-1 protein was initially identified as a Bcl-2-binding protein. It was reported to enhance Bcl-2 protection from cell death, suggesting that BAG-1 represents a new type of anti-cell death gene. Moreover, recent study has shown that BAG-1 can enhance the proliferation of neuronal precursor cells, attenuate the growth inhibition induced by siah1. However, its function and expression in the central nervous system lesion are not been understood very well. In this study, we performed a traumatic brain injury (TBI) model in adult rats and investigated the dynamic changes of BAG-1 expression in the brain cortex. Double immunofluorescence staining revealed that BAG-1 was co-expressed with NEURON and glial fibrillary acidic protein (GFAP). In addition, we detected that proliferating cell nuclear antigen had the co-localization with GFAP, and BAG-1. All our findings suggested that BAG-1 might involve in the pathophysiology of brain after TBI.     

The expression changes of Numblike in rat brain cortex after traumatic brain injury

Numblike (Numbl) plays an important role in ependymal wall integrity and subventricular zone neuroblast survival. And Numbl is specifically expressed in the brain. However, its expression and function in the central nervous system lesion are still unclear. In this study, we performed a traumatic brain injury (TBI) model in adult rats and investigated the dynamic changes of Numbl expression in the brain cortex. Western blot and immunohistochemistry analysis revealed that Numbl was present in normal brain. It gradually decreased, reached the lowest point at day 3 after TBI, and then increased during the following days. Double immunofluorescence staining showed that Numbl immunoreactivity was found in neurons, but not astrocytes and microglia. Moreover, the 3rd day post injury was the apoptotic peak implied by the alteration of caspase-3. All these results suggested that Numbl may be involved in the pathophysiology of TBI and further research is needed to have a good understanding of its function and mechanism.     

Induction of angiogenesis related genes in the contralateral cortex with a rat three-vessel occlusion model

The bFGF/FGFR, VEGF/VEGFR and Angiopoietin/Tie receptor system are crucial for angiogenesis and vascular remodeling. With a rat focal cerebral ischemia model, we previously reported dramatic changes in the vascular density and angiogenesis related genes in the ipsilateral cortex after 60 minutes severe ischemia. While only a small increase in the capillary density was noted in the contralateral cortex with very mild ischemia. In the present study we further reported that only Tie-1 and VEGFR-2 mRNA were significantly changed in the contralateral cortex with a p value of 0.0001 and 0.0168, respectively, and the degree of changes were very small. Interestingly, in contrast to a huge increase in the ipsilateral cortex, Tie-1 mRNA was slowly decreased after the onset of ischemia and stayed below the basal level throughout the remaining periods studied. The mechanism and significance for this decrease is not presently clear. In contrast to the ipsilateral cortex, the Angpo-1/Angpo-2 mRNA ratio was also slightly dropped below the basal level in the contralateral side in most of the ischemia-reperfusion periods studied, which is in line with the notion that small decrease in Angpo-1/Angpo-2 mRNA ratio implied small vascular remodeling activity. It is very likely that increase in this Angpo-1/Angpo-2 ratio is crucial for remodeling into large vessels and increase in Tie-1 may be crucial for capillary density increasing. Nevertheless, the detailed mechanisms and significance of differential expression of these genes and relationship to vascular remodeling remain to be characterized.     

Upregulation of CBLL1 in rat brain cortex after lipopolysaccharide treated

CBLL1 (Casitas B-lineage lymphoma-transforming sequence-like protein 1) also known as Hakai, was originally identified as an E3 ubiquitin-ligase for the E-cadherin complex. Recent data have provided evidences for novel biological functional role of CBLL1 during tumor progression and other diseases. However, its distribution and function in the central nervous system (CNS) remains unclear. In this study, we found CBLL1 was significant up-regulation in cerebral cortex after LPS administration and immunofluorescent labeling indicated that CBLL1 was localized striking in the neurons. We also investigated co-staining of CBLL1 and active-caspase-3 and cyclin D1 in the cerebral cortex following LPS administration. Based on our data, we speculated that CBLL1 might play an important role in neuronal apoptosis following LPS administration and might provide a basis for the further study on its role in cell cycle re-entry in neuroinflammation in CNS.     

Upregulation of p21-activated Kinase 6 in rat brain cortex after traumatic brain injury

p21-activated Kinase 6 (PAK6) is a serine/threonine kinase belonging to the p21-activated kinase (PAK) family. PAK kinases are well-known regulators of a wide variety of cellular functions, including regulation of cytoskeleton rearrangement, cell survival, apoptosis and the mitogen-activated protein kinase signaling pathway. To elucidate the expressions and possible functions of PAK6 in central nervous system (CNS) lesion and repair, we performed a traumatic brain injury (TBI) model in adult rats. Western blot analysis revealed that PAK6 level significantly increased at day 3 after damage, and then declined during the following days. Besides, double immunofluorescence staining showed PAK6 was primarily expressed in the neurons and a few of glial cells in the normal group. While after injury, the expression of PAK6 was increased significantly in the astrocytes and neurons, and the astrocytes had largely proliferated. We also examined the expression of proliferating cell nuclear antigen (PCNA) whose change was correlated with the expression of PAK6. Importantly, double immunofluorescence staining revealed that cell proliferation evaluated by PCNA appeared in many PAK6-expressing cells at day 3 after injury. In addition, injury-induced expression of PAK6 was co-labeled by active caspase-3 during neuronal apoptosis after injury. Collectively, we hypothesized PAK6 may play important roles in CNS pathophysiology after TBI and further research is needed to have a good understanding of its function and mechanism.     

Visceral field of the rat insular cortex

Structural-functional organisation of the cortical insular area relating to processes of the visceral functions control, was analysed. Representation of gastrointestinal, respiratory, and cardiovascular systems in the area, is given. Sites of respective neuronal groups and specifics of their spatial organisation within the area, were found. The data obtained suggest a scheme of the rat insular cortex's visceral field.     

Circadian oscillators in the mouse brain: molecular clock components in the neocortex and cerebellar cortex

The circadian timekeeper of the mammalian brain resides in the suprachiasmatic nucleus of the hypothalamus (SCN), and is characterized by rhythmic expression of a set of clock genes with specific 24-h daily profiles. An increasing amount of data suggests that additional circadian oscillators residing outside the SCN have the capacity to generate peripheral circadian rhythms. We have recently shown the presence of SCN-controlled oscillators in the neocortex and cerebellum of the rat. The function of these peripheral brain clocks is unknown, and elucidating this could involve mice with conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje and granular cell layers of the cerebellar cortex of the mouse brain. Among these, Per1, Per2, Cry1, Arntl, and Nr1d1 exhibit circadian rhythms suggesting that local running circadian oscillators reside within neurons of the mouse neocortex and cerebellar cortex. The temporal expression profiles of clock genes are similar in the neocortex and cerebellum, but they are delayed by 5 h as compared to the SCN, suggestively reflecting a master–slave relationship between the SCN and extra-hypothalamic oscillators. Furthermore, ARNTL protein products are detectable in neurons of the mouse neocortex and cerebellum, as revealed by immunohistochemistry. These findings give reason to further pursue the physiological significance of circadian oscillators in the mouse neocortex and cerebellum.     

Phosphoinositide metabolism in sections of the cortex of the large hemisphere of the brain in anoxia]

Depolarization (an increased concentration of KCL in the medium) has been investigated for its effect on the content and turnover rate of phospholipid phosphorus from the rat brain cortex slice under normal oxygen supply and under anoxia. It is shown that anoxia results in a small increase of phosphatidyl-inositol-4.5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP) content and in the depression of the turnover rate of all the phosphoinositides. Depolarization leads to a decrease in PIP2 concentration with a simultaneous increase in their turnover rate, these results being more expressed under anoxia. The development of depolarization by the 5th min. of anoxia in vivo leads, most probably, to the enhanced PIP2 breakdown, that is to a progressive decrease in their content.     

Depression of evoked potentials in rat thalamic ventro-basal complex and somatosensory cortex after reticular stimulation

Experiments on unanesthetized rats immobilized with D-tubocurarine showed that electrical stimulation (100/sec) of the central gray matter and the mesencephalic and medullary reticular formation considerably depressed potentials in the somatic thalamic relay nucleus and somatosensory cortex evoked by stimulation of the forelimb or medial lemniscus. The mean threshold values of the current used for electrical stimulation of these structures did not differ significantly and were 70 (20–100), 100 (20–120), and 120 (50–200) µA, respectively. On comparison of the amplitude-temporal characteristics of inhibition of evoked potentials during electrical stimulation of the above-mentioned structures by a current of twice the threshold strength, no significant differences were found. Immediately after the end of electrical stimulation the amplitude of the cortical evolved potential and the post-synaptic components of the thalamic evoked potential was 50–60% (P<0.01) below the control values. The duration of this depression varied from 0.5 to 1 sec. An increase in the intensity of electrical stimulation of brain-stem structures to between three and five times the threshold led to depression of the presynaptic component of the thalamic evoked potential also. Depression of the evoked potential as described above was found with various ratios between the intensities of conditioning and testing stimuli.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 8, No. 5, pp. 467–475, September–October, 1976.     

Restoration of contralateral representation in the mouse somatosensory cortex after crossing nerve transfer

Avulsion of spinal nerve roots in the brachial plexus (BP) can be repaired by crossing nerve transfer via a nerve graft to connect injured nerve ends to the BP contralateral to the lesioned side. Sensory recovery in these patients suggests that the contralateral primary somatosensory cortex (S1) is activated by afferent inputs that bypassed to the contralateral BP. To confirm this hypothesis, the present study visualized cortical activity after crossing nerve transfer in mice through the use of transcranial flavoprotein fluorescence imaging. In naïve mice, vibratory stimuli applied to the forepaw elicited localized fluorescence responses in the S1 contralateral to the stimulated side, with almost no activity in the ipsilateral S1. Four weeks after crossing nerve transfer, forepaw stimulation in the injured and repaired side resulted in cortical responses only in the S1 ipsilateral to the stimulated side. At eight weeks after crossing nerve transfer, forepaw stimulation resulted in S1 cortical responses of both hemispheres. These cortical responses were abolished by cutting the nerve graft used for repair. Exposure of the ipsilateral S1 to blue laser light suppressed cortical responses in the ipsilateral S1, as well as in the contralateral S1, suggesting that ipsilateral responses propagated to the contralateral S1 via cortico-cortical pathways. Direct high-frequency stimulation of the ipsilateral S1 in combination with forepaw stimulation acutely induced S1 bilateral cortical representation of the forepaw area in naïve mice. Cortical responses in the contralateral S1 after crossing nerve transfer were reduced in cortex-restricted heterotypic GluN1 (NMDAR1) knockout mice. Functional bilateral cortical representation was not clearly observed in genetically manipulated mice with impaired cortico-cortical pathways between S1 of both hemispheres. Taken together, these findings strongly suggest that activity-dependent potentiation of cortico-cortical pathways has a critical role for sensory recovery in patients after crossing nerve transfer.     

Structural basis of the intracortical synchronization of epileptic potentials in the sensomotor region of the rat neocortex

In control rats, penicillin-induced epileptiform discharges were completely synchronous in the neocortex sites at a distance of up to 4 mm from each other. Number of the cells decreased by 45.5% during 90 days in isolated cortical slabs and the synchronisation disappeared. The data obtained show that the loss of large pyramidal neurones of the layer V entailed a loss of the spatial synchronisation. The main axonal collaterals of large pyramidal neurones of the layer V could be followed horizontally for a distance of up to 2 mm in the somatosensory cortex. The neuronal network formed by the large pyramidal neurones of the layer V seems to provide a spatial synchronisation in the neocortex.