Epilepsy is a prevalent and chronic neurological disorder marked by recurring, uncontrollable seizures of the brain. Chronic or repeated seizures produce memory problems and induce damage to different brain regions. Histamine has been reported to have neuroprotective effects. Betahistine is a histamine analogue. The current research investigated the effects of convulsions on the cerebral cortex and hippocampus of adult male albino mice and assessed the possible protective effect of betahistine. Four groups of 40 adult male mice were organized: control, betahistine (10 mg/kg/day), pentylenetetrazole (PTZ) (40 mg/kg/ on alternate days), and Betahistine-PTZ group received betahistine 1 h before PTZ. PTZ induced a substantial rise in glutamate level and a considerable decrease in histamine level. Structural changes in the cerebral cortex and cornu ammonis (CA1) of the hippocampus were detected in the pattern of neuron degeneration. Some neurons were shrunken with dark nuclei, and others had faintly stained ones. Focal accumulation of neuroglial cells and ballooned nerve cells of the cerebral cortex were also detected. Cleaved caspase-3, glial fibrillary acidic protein, and ionized calcium-binding adaptor molecule 1 showed substantial increases, while synaptophysin expression was significantly reduced. Interestingly, these changes were less prominent in mice pretreated with betahistine. In conclusion, betahistine had shown neuroprotective properties against brain damage induced by convulsions.

Listeriosis is a disease that is induced by infection with the Gram-positive bacterium Listeria monocytogenes. Much is still unknown about the pathogenesis of encephalitic listeriosis. We aimed to identify the contribution of glial fibrillary acidic protein (GFAP), epithelial cadherin (E-cadherin), S100, and acute-phase proteins (APPs) in pathogenesis, clinical and preclinical diagnosis of natural cases of encephalitic listeriosis. Of 1,325 Ossimi sheep, 64 were suspected of having listeriosis from 2018 to 2020. Prospective cohort evaluation of clinical and postmortem findings was performed, in addition to bacterial isolation, the measurement of APPs in serum and cerebrospinal fluid (CSF), and the histopathological and immunohistochemical evaluation of GFAP, S100, and E-cadherin. Infected sheep showed nervous symptoms ranging from neck stretching to complete paralysis. APPs were significantly increased in the CSF of both clinically and preclinically diseased animals; however, serum APPs were only significantly increased in clinically diseased animals. Histopathological evaluation revealed microabscesses, meningoencephalitis, and perivascular cuffing of the brainstem of infected sheep. Immunohistochemical investigations revealed strong expression of GFAP and S100 in necrotic areas and negative expression of E-cadherin. The measurement of CSF APPs could be useful in the preclinical diagnosis of sheep listeriosis. GFAP and S100 proteins could be involved in the pathogenesis of listeriosis; however, E-cadherin does not appear to be involved.

The present study aims to investigate the efficacy of intravenously injected mesenchymal stem cells (MSCs) in treating neuropathic pain either before or after its induction by a chronic constriction injury (CCI) model. Rats were divided into four groups: control group, neuropathic group, and treated groups (pre and postinduction) with i.v. mononuclear cells (106 cell/mL). For these rats, experimental testing for both thermal and mechanical hyperalgesia was evaluated. The cerebral cortex of the rats was dissected, and immunohistochemical analysis using anti-proliferating cell nuclear antigen (PCNA), CD117, nestin, and glial fibrillary acidic protein was performed. Our results showed that a single injection of MSCs (either preemptive/or post-CCI) produced equipotent effects on allodynia, mechanical hyperalgesia, and thermal response. Immunohistochemical analysis showed that the stem cells have reached the cerebral cortex. The injected group with MSCs before CCI showing few stem cells expressed PCNA, CD117, and nestin in the cerebral cortex. The group injected with MSCs after CCI, showing numerous recently proliferated CD117-, nestin-, PCNA-positive stem cells in the cerebral cortex. In conclusion, our findings demonstrate that the most probable effect of i.v. stem cells is the central anti-inflammatory effect, which opens concerns about how stem cells circulating in systemic administration to reach the site of injury.

Teleosts exhibit enormous heterogeneity in brain morphology, especially in the patterns of the organization of cerebellum. The cerebellum of a red-tail shark that we analyzed was well-developed and included three main divisions: the valvula cerebelli, the corpus cerebelli, and the vestibulolateral lobe. Characteristically, the cerebellar cortex contained three well-distinct layers: an outer molecular, intermediate ganglionic, and inner granular layer. The ganglionic layer possessed irregularly arranged Purkinje cells and eurydendroid cells that extended their processes into the molecular layer. Both Purkinje cells and eurydendroid cells showed immunoreactivity for iNOS2. Moreover, astrocytes in the cerebellum showed the expression of glial fibrillary acidic protein. The most striking observation in the cerebellum of shark was the lack of deep cerebellar nuclei and a well-identified white matter. On the other hand, the gray substance in the spinal cord displays a characteristic pattern in its organization, in which the dorsal horns lie quite close together, giving the gray substance the shape of an inverted Y and possessing large neurons. Notably, the white matter possessed myelinated nerve fibers. The current study provides the first report on the organization of layers and neurons in the cerebellum and spinal cord of red-tail shark. This research will contribute to the neuroanatomy and evolutionary studies of the brain of Cyprinidae.

Reduction of blood flow to the rat retina was achieved by either clamping both carotid arteries briefly (24 min) or combining clamping of the carotid arteries with permanent occlusion of the vertebral arteries. Analysis of retinas 6 days after operations showed that GFAP immunoreactivity is expressed throughout the retinal Müller cells, although this was variable in retinas from animals where only the carotid arteries were clamped. GFAP immunoreactivity was not associated with retinal Müller cells from control animals and no obvious neuronal damage was observed in retinas from operated animals. These data suggest that Müller-cell GFAP expression may be used as an index to follow possible processes leading to an ischemic insult.

NG2 cells represent a unique glial cell population that is distributed widely throughout the developing and adult CNS and is distinct from astrocytes, mature oligodendrocytes and microglia. The ability of NG2 cells to differentiate into myelinating oligodendrocytes has been documented in vivo and in vitro. We reported recently that NG2 cells in the forebrain differentiate into myelinating oligodendrocytes but into a subpopulation of protoplasmic astrocytes (Zhu et al., 2008). However, the in vivo fate of NG2 cells in the spinal cord and cerebellum has remained unknown. To investigate the fate of NG2 cells in caudal central nervous system (CNS) regions in vivo, we examined the phenotype of cells that express EGFP in mice that are double transgenic for NG2CreBAC and the Cre reporter Z/EG. The fate of NG2 cells can be studied in these mice by permanent expression of EGFP in cells that have undergone Cre-mediated recombination in NG2 cells. We find that NG2 cells give rise to oligodendrocytes in both gray and white matter of the spinal cord and cerebellum, and to protoplasmic astrocytes in the gray matter of the spinal cord. However, NG2 cells do not give rise to astrocytes in the white matter of the spinal cord and cerebellum. These observations indicate that NG2 cells serve as precursor cells for oligodendrocytes and a subpopulation of protoplasmic astrocytes throughout the rostrocaudal axis of the CNS.

Astroglia comprise an extremely morphologically diverse cell type that have crucial roles in neural development and function. Nonetheless, distinct regions of the CNS have traditionally been defined by the phenotypic characteristics and connectivity of neurons. In a complementary fashion, we present evidence that discrete regions of the adult CNS can be delineated based solely on the morphology, density and proliferation rates of astroglia.We used transgenic hGFAP-GFP mice in which robust expression of GFP in adult astroglia enables detailed morphological characterization of this diversely heterogeneous cell population with 3D confocal microscopy. By using three complementary methods for labeling adult astroglia (hGFAP-GFP expression, and GFAP and S100β immunostaining), we find that there is a remarkably diverse, regionally stereotypical array of astroglial morphology throughout the CNS, and that discrete anatomical regions can be defined solely on the morphology of astroglia within that region. Second, we find that the density of astroglia varies dramatically across the CNS, and that astroglial density effectively delineates even the sub-regions of complex structures, such as the thalamus. We also find that regional astroglial density varies depending on how astroglia are labeled. To quantify and illustrate these broad differences in astroglial density, we generated an anatomical density atlas of the CNS. Third, the proliferation rate, or mitotic index, of astroglia in the adult CNS also effectively defines anatomical regions. These differences are present regardless of the astroglial-labeling method used. To supplement our atlas of astroglial density we generated an atlas of proliferation density for the adult CNS. Together, these studies demonstrate that the morphology, density and proliferation rate of astroglia can independently define the discrete cytoarchitecture of the adult mammalian CNS, and support the concept that regional astroglial heterogeneity reflects important molecular and functional differences between distinct classes of astroglia, much like the long-accepted heterogeneity of neuronal populations.

Little is known about the functional connectivity between astrocytes in the CNS. To explore this issue we photo-released glutamate onto a single astrocyte in murine hippocampal slices and imaged calcium responses. Photo-release of glutamate causes a metabotropic glutamate receptor (mGluR)-dependent increase in internal calcium in the stimulated astrocyte and delayed calcium elevations in neighboring cells. The delayed elevation in calcium was not caused by either neuronal activity following synaptic transmission or by glutamate released from astrocytes. However, it was reduced by flufenamic acid (FFA), which is consistent with a role for adenosine triphosphate (ATP) release from astrocytes as an intercellular messenger. Exogenous ligands such as ATP (1 µM) increased the number of astrocytes that were recruited into coupled astrocytic networks, indicating that extracellular accumulation of neurotransmitters modulates neuronal excitability, synaptic transmission and functional coupling between astrocytes.