When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.
Astrocytes ; Axons/pathology* ; Cicatrix/pathology* ; Gliosis/pathology* ; Humans ; Medicine, Chinese Traditional ; Nerve Regeneration ; Stroke/drug therapy*

OBJECTIVE: The advent of high resolution magnetic resonance imaging(MRI) contributed to the preoperative localization of epileptogenic area. Even the discrete lesion visualized on MRI can be often correlated with seizure onset zone. If MRI does not, however, show any lesions in the extratemporal epilepsy, it imposes a significant challenge. This study is designed to evaluate the surgical treatment of extratemporal lobe epilepsy in which MRI does not show any lesion, to define the surgical strategy and to investigate the underlying pathology. METHODS: We studied the nineteen patients with MRI-negative extratemporal epilepsy who underwent resective surgery after careful preoperative investigation between 1993 and 1995. RESULTS: Scalp EEG could not lateralize the epileptogenic foci in 9 patients. Intracranial EEG recording was performed in all patients with successful localization: depth electrode study in 12, and subdural grid and strip study in 7 patients. Resection was performed in frontal(n=14), in parietal(n=3), and in multilobar area(n=2). Pathological findings comprised cortical dysplasia in 10, gliosis in 7, and collagenoma in one patients. The surgical outcome was classified as seizure free in 10, rare seizures in 2, significant reduction in 5, and no change in 2 patients. CONCLUSION: MRI-invisible extratemporal epilepsy can be managed surgically with promising results. Cortical dysplasia and gliosis are two major pathological findings in this context though MRI does not demonstrate any lesions.
Electrodes ; Electroencephalography ; Epilepsy* ; Gliosis ; Humans ; Magnetic Resonance Imaging ; Malformations of Cortical Development ; Pathology ; Scalp ; Seizures

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

PURPOSE: Epilepsy surgery has become increasingly available in children with medically intractable epilepsy including temporal lobe epilepsy(TLE). TLE in children, however, has many different clinical and electrophysiologic characteristics which make presurgical evaluation difficult. The aim of this study is to evaluate the electroencephalographic(EEG) features which might be one of the predictors of postsurgical seizure outcomes in TLE. METHODS: Standard EEG, video-EEG, subdural or depth EEG were investigated in 12 children who underwent anterior temporal lobectomy, and their seizure semiology, MRI, and pathologic findings were also reviewed. Postsurgical seizure outcomes were divided into favorable(class I, II) and unfavorable(class III, IV) groups by using the Engel's classification. RESULTS: Half of the patients showed favorable outcomes, whose pathologic findings revealed hippocampal sclerosis or gliosis. Such pathologic findings were not demonstrated in MRI. Interictal epileptiform discharges were concordant with the location of the ictal onset in only 2 cases of the favorable outcomes. For the other 4 cases in the favorable group, focal ictal onset patterns were clearly evident in video-EEG monitorings or invasive EEG studies. Six cases in the unfavorable group showed unlocalized or multifocal interictal or ictal discharges -extratemporal, bitemporal or generalized epileptic activities- even in the invasive EEG studies. Five of them revealed cortical dysplasia in the pathology. CONCLUSION: The postsurgical seizure outcomes of hippocampal sclerosis or gliosis were more favorable than those of cortical dysplasia. Invasive EEG recordings should be considered for the localization of epileptic foci in the presurgical evaluation of children with intractable TLE.
Anterior Temporal Lobectomy ; Child* ; Classification ; Electroencephalography ; Epilepsy ; Gliosis ; Humans ; Magnetic Resonance Imaging ; Malformations of Cortical Development ; Pathology ; Sclerosis ; Seizures ; Temporal Lobe*

Binswanger's disease (BD) is an illness of hypertensive elderly patients characterised clinically by disorders of memory, mood and cognition; focal motor signs; and less often, a pseudobulbar syndrome with deterioration of gait and sphincter control. The illness is usually slowly progressive. The important pathological features of BD are widespread degeneration in the deep white matter with diffuse, patchy axonal and myelin loss, and gliosis. The more diffuse lesions in the centrum semiovale have been related to myelin rarefaction that spares the U-fibers. The MRI appearance of BD is multiple confluent white matter lesions of various sizes, many of which are quite small and concentrated around the basal ganglia and periventricular areas. We report an autopsy case of Binswanger's disease associated with Alzheimer's pathology.
Aged ; Alzheimer Disease ; Autopsy* ; Axons ; Basal Ganglia ; Cognition ; Dementia, Vascular* ; Gait ; Gliosis ; Humans ; Magnetic Resonance Imaging ; Memory ; Myelin Sheath ; Pathology* ; Pseudobulbar Palsy

We investigated a topographical distribution of managanese, and immunohistochemical density of tyrosine hydroxylase (TH), and histopathologic findings in globus pallidus and substantia nigra according to manganese dose and time course in the brain of rats which received MnCl2 intravenously. Topographical distribution of manganese was also investigated after injection of FeCl2. The manganese concentrations of brain in control and experimental group were highest in pituitary gland and thalamus, and lowest in the cerebral cortex. The manganese concentration of blood was increased proportionally to the dose administered, and the biological half-life of blood manganese was between 21 and 42 days. The manganese concentrations of brain were increased proportionally to the dose, and increase rate was highest in olfactory bulb, and the biological half-lives of brain manganese ranged from 42 days to 90 or more days; the longest were observed in pituitary gland, medulla oblongata and cerebral cortex. In case of administration of FeCl2, the manganese concentrations of brain were higher than that of control group in dose of 2.5 mg/kg, and decreased proportionally to the administered dose, resulting in lower level compared with control group in high dose of FeCl2 administered. Significantly decreased number of nerve cell and increased gliosis in globus pallidus were observed in experimental group, which were closely correlated with the duration after manganese injection, but no significant change of number of nerve cell expressing TH and gliosis were observed in substantia nigra. Density of immunohistochemical reaction for TH in globus pallidus made little difference between control and experimental group. These results suggest that pathology of manganese intoxication is caused by the loss of nerve cells in globus pallidus, and closely correlated with the duration after manganese exposure.
Animals ; Brain* ; Cerebral Cortex ; Gliosis ; Globus Pallidus ; Half-Life ; Manganese* ; Medulla Oblongata ; Neurons ; Olfactory Bulb ; Pathology ; Pituitary Gland ; Rats* ; Substantia Nigra ; Thalamus ; Tyrosine 3-Monooxygenase

OBJECTIVETo investigate the immunohistochemical expression of isocitrate dehydrogenase 1 gene (IDH1) R132H in glioma and its diagnostic utility.

METHODSImmunohistochemical study of IDH1R132H expression was performed on formalin-fixed paraffin-embedded tissue samples of 75 gliomas, including 33 cases of grade II, 20 cases of grade III and 22 cases of grade IV tumors. Six cases of pilocytic astrocytoma and 12 cases of gliosis were used as controls.

RESULTSNineteen in 33 cases of grade II (57.6%), 8 in 20 cases of grade III (40.0%), 6 in 22 cases of grade IV (27.3%) showed positive cytoplasmic staining of IDH1R132H. Scattered invasive glioma cells at the tumor periphery also expressed IDH1R132H. Gliomas involving the frontal lobe showed more strong IDH1R132H staining. In contrast, none of the pilocytic astrocytomas and gliosis showed IDH1R132H staining. Moreover, the rate of p53 immunopositivities were 42.4% (14/33) in grade II, 65.0% (13/20) in grade III and 77.3% (17/22) in grade IV gliomas. There were no statistic correlations between expression of IDH1R132H and p53.

CONCLUSIONIDH1R132H tends to express preferentially in low-grade gliomas, and it thus may serve as a valuable marker in distinguishing low grade gliomas from gliosis.

Adolescent ; Adult ; Aged ; Astrocytoma ; metabolism ; pathology ; Brain Neoplasms ; metabolism ; pathology ; Child ; Diagnosis, Differential ; Female ; Glioma ; metabolism ; pathology ; Gliosis ; metabolism ; pathology ; Humans ; Isocitrate Dehydrogenase ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Tumor Suppressor Protein p53 ; metabolism ; Young Adult

OBJECTIVETo understand the infectious characteristics of a hamster-adapted scrapie strain 263K with five different routes of infection including intracerebral (i.c.), intraperitoneal (i.p.), intragastrical (i.g.), intracardiac and intramuscular (i.m.) approaches.

METHODSHamsters were infected with crude- or fine-prepared brain extracts. The neuropathological changes, PrP(Sc) deposits, and patterns of PK-resistant PrP were analyzed by HE stain, immnunohistochemistry (IHC) assay and Western blot. Reactive gliosis and neuron loss were evaluated by glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE) specific IHC.

RESULTSThe animals inoculated in i.m. and i.p. ways with crude PrP(Sc) extracts showed clinical signs at the average incubation of 69.2 +/- 2.8 and 65.5 +/- 3.9 days. Inoculation in i.c. and intracardiac ways with fine PrP(Sc) extracts (0.00035 g) caused similar, but relative long incubation of around 90 days. Only one out of eight hamsters challenged in i.g. way with low dosage (0.01 g) became ill after a much longer incubation (185 d), while all animals (4/4) with high dosage (0.04 g) developed clinical signs 105 days postinfection. The most remarkable spongiform degeneration and PrP(Sc) deposits were found in brain stem among the five challenge groups generally. The number of GFAP-positive astrocytes increased distinctly in brain stems in all infection groups, while the number of NSE-positive cells decreased significantly in cerebrum, except i.c. group. The patterns of PK-resistant PrP in brains were basically identical among the five infection routes.

CONCLUSIONTypical TSE could be induced in hamsters by inoculating strain 263K in the five infection ways. The incubation periods in bioassays depend on infective dosage, administrating pathway and preparation of PrP(Sc). The neuropathological changes and PrP(Sc) deposits seem to be related with regions and inoculating pathways.

Administration, Oral ; Animals ; Blotting, Western ; Brain ; metabolism ; pathology ; Cricetinae ; Gliosis ; metabolism ; pathology ; Immunohistochemistry ; Injections, Intramuscular ; Injections, Intraperitoneal ; Injections, Intraventricular ; Neurons ; enzymology ; pathology ; Phosphopyruvate Hydratase ; metabolism ; Prions ; administration & dosage ; metabolism ; pathogenicity ; Scrapie ; metabolism ; pathology

BACKGROUNDIn response to the injury of the central nervous system (CNS), the astrocytes upregulate the expression of glial fibrillary acidic protein (GFAP), which largely contributes to the reactive gliosis after brain injury. The regulatory mechanism of this process is still not clear. In this study, we aimed to compare the ephrin-B2 deficient mice with the wild type ones with regard to gliosis after traumatic brain injury.

METHODSWe generated ephrin-B2 knockout mice specifically in CNS astrocytes. Twelve mice from this gene-knockout strain were randomly selected along with twelve mice from the wild type littermates. In both groups, a modified controlled cortical impact injury model was applied to create a closed traumatic brain injury. Twenty-eight days after the injury, Nissl staining and GFAP immunofluorescence staining were used to compare the brain atrophy and GFAP immunoreactivity between the two groups. All the data were analyzed by t-test for between-group comparison.

RESULTSWe successfully set up the conditional ephrin-B2 knockout mice strain, which was confirmed by genotyping and ephrin-B2/GFAP double staining. These mice developed normally without apparent abnormality in general appearance. Twenty-eight days following brain injury, histopathology revealed by immunohistochemistry showed different degrees of cerebral injuries in both groups. Compared with wild-type group, the ephrin-B2 knockout group exhibited less brain atrophy ratio for the injured hemispheres (P = 0.005) and hippocampus (P = 0.027). Also the wild-type group demonstrated greater GFAP immunoreactivity increment within hippocampal regions (P = 0.008).

CONCLUSIONSThe establishment of conditional ephrin-B2 knockout mice provides us with a new way to explore the role of ephrin-B2 in astrocytes. Our findings revealed less atrophy and GFAP immunoreactivity in the knockout mice strain after traumatic brain injury, which implied ephrin-B2 could be one of the promoters to upregulate gliosis following brain injury.

Animals ; Atrophy ; Brain ; pathology ; Brain Injuries ; complications ; pathology ; Ephrin-B2 ; deficiency ; physiology ; Glial Fibrillary Acidic Protein ; Gliosis ; etiology ; Immunohistochemistry ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins ; analysis

Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter.
Adventitia ; Amyloid ; Arteries ; Arterioles ; Atrophy ; Basal Ganglia ; Brain ; Brain Ischemia ; CADASIL ; Cerebral Amyloid Angiopathy ; Cerebral Small Vessel Diseases ; Connective Tissue ; Edema ; Gliosis ; Humans ; Hypertension ; Hypertrophy ; Metalloproteases ; Muscle, Smooth ; Parents ; Pathology* ; Pons ; Stroke, Lacunar* ; Tunica Media