Glial Changes Research Articles

Biochemical abnormalities of the medial temporal lobe and medial prefrontal cortex in late-life depression

We utilized single-voxel 1H magnetic resonance spectroscopy (MRS) to investigate biochemical abnormalities related to late-life depression in the medial prefrontal cortex and medial temporal lobe. Fourteen elderly subjects whose depression responded to treatment and 12 nondepressed subjects were enrolled. Subjects were scanned using a GE 3.0 Tesla whole body MR scanner. Metabolite concentrations were quantified using the LC Model software and adjusted for CSF and ratio of gray to white matter. ANCOVA models tested for group differences while controlling for age and sex. Older previously depressed individuals showed significantly reduced concentrations of total N-acetyl aspartate (NAA), choline, and creatine in the prefrontal cortex and significantly elevated left medial temporal lobe concentrations of NAA and myo-inositol. There were no significant group differences in right temporal metabolite concentrations. The prefrontal cortex observations suggest that reduced neuronal, phospolipid, and energy metabolism is present even in clinically improved depression. In contrast, elevated NAA and myo-inositol concentrations in the left medial temporal lobe could be associated with neuronal and glial cell changes in the amygdala.

Effects of glutamate receptor activation on NG2-glia in the rat optic nerve.

NG2-glia are a substantial population of cells in the central nervous system (CNS) that can be identified by their specific expression of the NG2 chondroitin sulphate (CSPG). NG2-glia can generate oligodendrocytes, but it is unlikely this is their only function; indeed, they may be multipotent neural stem cells. Moreover, NG2-glia are a highly reactive cell type and a major function is to help form the axon growth inhibitory glial scar in response to CNS injury. The factors that regulate these diverse behaviours of NG2-glia are not fully resolved, but NG2-glia express receptors to the neurotransmitter glutamate, which has known potent effects on other glia. Here, we have examined the actions of glutamate receptor activation on NG2-glia in the rat optic nerve, a typical CNS white matter tract that does not contain neuronal cell bodies. Glutamate induces an increase in [Ca(2+)](i) in immuno-identified NG2-glia in situ and in vitro. In addition, we examined the effects of glutamate receptor activation in vivo by focal injection of the glutamate receptor agonist kainate into the optic nerve; saline was injected in controls. Changes in glial and axonal function were determined at 7 days post injection (dpi), by immunohistochemistry and electrophysiological measurement of the compound action potential (CAP). Injection of kainate resulted in a highly localized 'injury response' in NG2-glia, marked by dense labelling for NG2 at the lesion site, as compared to astrocytes, which displayed a more extensive reactive astrogliosis. Furthermore, injection of kainate resulted in an axonal conduction block. These glial and axonal changes were not observed following injection of saline vehicle. In addition, we provide evidence that endogenous glutamate induces calcium-dependent phosphorylation of extracellular signal-regulated kinases (ERK1/2), which may provide a potential mechanism by which glutamate-mediated changes in raised intracellular calcium could regulate the observed gliosis. The results provide evidence that activation of AMPA-kainate type ionotropic glutamate receptors evoke raised calcium in NG2-glia and induces an injury response in NG2-glia.

Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis

Astrocytes, the most abundant glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity. In response to a brain injury, astrocytes proliferate and become hypertrophic with an increased expression of intermediate filament proteins. This process is collectively referred to as reactive astrocytosis. Lipocalin 2 (lcn2) is a member of the lipocalin family that binds to small hydrophobic molecules. We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. lcn2 expression and secretion increased after inflammatory stimulation in cultured astrocytes. Forced expression of lcn2 or treatment with LCN2 protein increased the sensitivity of astrocytes to cytotoxic stimuli. Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. In zebrafishes, forced expression of rat lcn2 gene increased the number and thickness of cellular processes in GFAP-expressing radial glia cells, suggesting that lcn2 expression in glia cells plays an important role in vivo. Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo.

Dose-related immunohistochemical and ultrastructural changes after oral methylphenidate administration in cerebrum and cerebellum of the rat

Methylphenidate is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder of children and young adults. Our aim is to investigate dose-dependent dopamine-2 receptor and glial fibrillary acidic protein expression and ultrastructural changes of the rat brain, to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. In this study, 27 female prepubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) were treated orally with methylphenidate dissolved in saline solution for 5 days per week during 3 months. At the end of the third month, tissues were removed and sections were collected for immunohistochemical and ultrastructural studies. We believe that methylphenidate causes dose-related activation of the dopaminergic system in several brain regions especially in ventral tegmental area and also causing neuronal degeneration and capillary wall structural changes such as basal membrane thickness and augmentation of the pinostatic vesicle in the endothelial cells. Also, increased dose of Ritalin is inducing astrocytes hypertrophy especially astrogliosis in pia-glial membrane and this is the result of the degenerative changes in prefrontal cortex region due to high dose methylphenidate administration. The dose-related accumulation of the astrocytes in capillary wall might well be a consequence of the need for nutrition of the neuronal tissue, due to transport mechanism deficiency related to neuronal and vascular degeneration. Thus, we believe that the therapeutic dose of methylphenidate must be kept in minimum level to prevent ultrastructural changes.

Gene, Cell, and Axon Changes in the Familial Amyotrophic Lateral Sclerosis Mouse Sensorimotor Cortex

Lower motoneuron abnormalities have been extensively documented in the murine model of familial amyotrophic lateral sclerosis, whereas information on corticospinal neurons in these mice is very limited. We investigated 1) mRNA levels of inflammation-related molecules in the deep layers in which corticospinal neurons reside, 2) corticospinal neurons labeled from tracer injections in the corticospinal tract at the cervical level, 3) axonal damage revealed by beta-amyloid precursor protein accumulation, and 4) glial cell activation in the sensorimotor cortex of presymptomatic and end-stage superoxide dismutase (SOD)-1 (G93A) mice. We demonstrated induction of inflammatory gene transcripts in the deep layers, early and progressive shrinkage of corticospinal cell bodies and activation of surrounding astrocytes and microglia with upregulation of major histocompatibility complex class I antigen. Accumulation of beta-amyloid precursor protein in proximal axonal swellings indicating axonal injury was also evident at the terminal stage in the motor cortex and internal capsule. Glial and axon changes were not observed elsewhere in the cortex. These data reveal that the entire motor circuit is affected in this murine amyotrophic lateral sclerosis model as it is in human amyotrophic lateral sclerosis. Sensorimotor cortical inflammation and progressive corticospinal cell body and fiber damage may reflect transsynaptic signaling of damage from lower motoneurons.

The level of butyrylcholinesterase activity increases and the content of the mRNA remains unaffected in brain of senescence-accelerated mouse SAMP8

Looking at cholinesterases (ChEs) changes in age-related mental impairment, the expression of ChEs in brain of senescence accelerated-resistant (SAMR1) and senescence accelerated-prone (SAMP8) mice was studied. Acetylcholinesterase (AChE) activity was unmodified and BuChE activity increased twofold in SAMP8 brain. SAMR1 brain contained many AChE-T mRNAs, less BuChE and PRiMA mRNAs and scant AChE-R and AChE-H mRNAs. Their content unchanged in SAMP8 brain. Amphiphilic ( G 4 A ) and hydrophilic ( G 4 H ) AChE and BuChE tetramers, besides amphiphilic dimers ( G 2 A ) and monomers ( G 1 A ) were identified in SAMR1 brain and their distribution was little modified in SAMP8 brain. Blood plasma does not seem to provide the excess of BuChE activity in SAMP8 brain; it probably arises from glial cell changes owing to astrocytosis.

Fourth Conference on Epileptogenesis, May 23–26, 2007, Pisa, Italy

Fourth Conference on Epileptogenesis, May 23–26, 2007, Pisa, Italy

AT1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen‐induced retinopathy

We investigated the effect of receptor blockade induced by an angiotensin II type-1 receptor antagonist (AT(1)-RB) on glial and vascular changes in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity (ROP). OIR was induced in Sprague-Dawley rats by exposure to 80% oxygen from postnatal (P) days 0-11, followed by 7 days in room air. Control animals were in room air for the entire duration. One cohort of OIR and control pups received the AT(1)-RB valsartan (40 mg/kg/day intraperitoneal) from P11 to P18. The vascular response was examined immunocytochemically using retinal wholemounts and vertical sections labeled with endothelial (Isolectin-B4) and pericyte (NG2, desmin) markers. Glial cell changes were assessed by measuring cell numbers and immunoreactivity (S100beta, connexin-26, and glial fibrillary acidic protein). OIR resulted in extensive intravitreal neovascularization and under-development of the outer vascular plexus. Pericyte numbers were not significantly affected in OIR, although pericyte-endothelial (desmin-IB4) interactions were impaired. Peripheral astrocyte degeneration occurred between P11 and P13 with prominent Müller cell reactivity at P18. Valsartan imparted a protective effect on glia and blood vessels in OIR. At P18, valsartan-treated OIR retinae showed significantly greater astrocyte survival, improved revascularization of the retina, and reduced preretinal neovascularization and Müller cell reactivity. This study identifies a glio-vascular protective effect with AT(1)-RB in OIR.

Rapid astrocyte and microglial activation following pilocarpine‐induced seizures in rats

Astrocyte and microglial activation occurs following seizures and plays a role in epileptogenesis. However, the precise temporal and spatial response to seizures has not been fully examined. The pilocarpine model of temporal lobe epilepsy was selected to examine glial changes following seizures because morphological changes in the hippocampus closely mimic the human condition. Astrocytic and microglial changes in the hippocampus were examined during the first 5 days after pilocarpine-induced seizures in rats by analyzing GFAP, Iba1 and S100B-immunolabeling in CA1, CA3, and the hilus. Also, 3-dimensional reconstructions of microglial cells from the hilus and granule cell layer were analyzed. Lastly, astrocyte hypertrophy was examined in the hilus using electron microscopy. At 1 day after seizures and continuing throughout the 5 days examined, hypertrophied Iba1-labeled microglial cells and glial fibrillary acidic protein (GFAP)-labeled astrocytes were observed. At 1 and 2 days after seizures, significantly greater Iba1 immunolabeling was observed in CA1, CA3, and the hilus. In addition, both the area of Iba1 labeled processes and the number of their endings were increased in the hilus beginning at 1 day after seizures. S100B-immunolabeling was significantly elevated in CA3 at 1 day, in CA3 and CA1 at 2 days, and in all three hippocampal regions at 3 days after seizures. Electron microscopy confirmed astrocytic hypertrophy and demonstrated astrocytic cell bodies in the location where glial endfeet normally appear on capillaries. The differential response patterns of astrocytes and microglial cells following pilocarpine-induced seizures may signify their detrimental role in neuroinflammation after seizures.

Cellular responses in the spinal cord during development of hypomyelination in the mv rat

The myelin vacuolation ( mv) rat is an autosomal recessive mutant characterized by hypomyelination and vacuole formation in the myelin throughout the central nervous system (CNS). Previous genetic studies have revealed a null mutation in attractin gene of the mv mutant rat. It has been known that mutation at the attractin locus results in myelin alterations, but their detailed pathogenesis is still unclear. In this study, we examined glial changes in the spinal cord of mv rats at 2, 4, 6, and 8 weeks of age and identified attractin-expressing cells in the rat spinal cord. No abnormality was found in the number and morphology of oligodendrocytes in mv rats at any of the ages examined, although the severity and extent of myelin disorder increased with age. Coincident with the myelin abnormalities, there was progressive astrogliosis from 2 weeks. Marked microglial activation was observed exclusively in the gray matter of mv rats from 6 weeks, coincident with severe myelin disruption. A double-labeling study demonstrated that attractin-expressing cells are mostly oligodendrocytes in the white matter of the spinal cord of wild-type rats, whereas no attractin-positive cells were detected in mv rats. Previous study demonstrated that Luxol fast blue staining pattern and immunoreactivity for myelin basic protein were decreased in mv rats. Therefore, this study indicates that the attractin defect results in oligodendrocyte dysfunction, and is associated with astrogliosis and microglial activation in mv rats. The data suggest that attractin may be directly involved in the function of oligodendrocytes in CNS myelination.

What Is the Present Pathogenetic Concept of Glaucomatous Optic Neuropathy?

Glaucomatous optic neuropathy implies loss of neural tissue, activation of glial cells, tissue remodeling, and change of blood flow. The blood flow reduction is not only secondary but has a primary component. Activation of astrocytes leads to an altered microenvironment. An unstable ocular perfusion, either due to IOP fluctuation or a disturbed autoregulation (due to primary vascular dysregulation syndrome) leads to a mild reperfusion injury. The superoxide (O 2 −) anion produced in the mitochondria of the axons, fuses with the nitric oxide (NO) diffusing from the astrocytes, leading to the damaging peroxynitrite (ONOO −). It is possible that the diffusion of endothelin and metalloproteinases to the surrounding of the optic nerve head leads to a local vasoconstriction and thereby increases the risk for venous occlusion and weakens the blood–brain barrier, which in extreme situations results in splinter hemorrhages. Activated retinal astrocytes can be visualized clinically. The involvement of primary vascular dysregulation in the pathogenesis of glaucomatous optic neuropathy may explain why women, as well as Japanese, suffer more often from normal-tension glaucoma.

Developmental changes in content of glial marker proteins in rats exposed to protein malnutrition

Pre- and postnatal protein malnutrition (PMN) adversely affects the developing brain in numerous ways, but only a few studies have investigated specific glial parameters. This study aimed to evaluate specific glial changes of rats exposed to pre and postnatal PMN, based on glial fibrillary acidic protein (GFAP) and S100B immunocontents as well as glutamine synthetase (GS), in cerebral cortex, hippocampus, cerebellum and cerebrospinal fluid, on the 2nd, 15th and 60th postnatal days. We found increases in GFAP, S100B and GS in the cerebral cortex at birth, suggesting an astrogliosis. Hippocampus and cerebellum also exhibited this profile at birth. However, a significant interaction between age and diet in postnatal life was observed only in the S100B of the cerebral cortex. No changes in the content of GFAP and S100B and GS activity were found on the 60th postnatal day in malnourished rats. In contrast, following an increase in the levels of S100B in the cerebrospinal fluid, during the early developmental stages, levels remained elevated on the 60th postnatal day. Our data support the concept of astrogliosis at birth, induced by PMN, and involve extracellular-regulated kinase activation. Specific alterations in cerebral cortex emphasize the regional vulnerability of the brain to malnutrition; some alterations were observed only at birth (e.g. GFAP); others were observed on the 2nd and 15th post-natal days (e.g. ERK phosphorylation). Taken together, transient and persistent alterations (e.g. elevated extracellular levels of S100B) suggest some brain damage or a risk of brain diseases in rats exposed to PMN.

Late Onset Psychosis in Survivors of Pediatric Central Nervous System Malignancies

Late Onset Psychosis in Survivors of Pediatric Central Nervous System Malignancies

Neuronal and glial cell changes are determined by retinal vascularization in retinopathy of prematurity

We have characterized the vascular, neuronal, and glial changes in oxygen-induced retinopathy, a model of retinopathy of prematurity (ROP). Newborn Sprague-Dawley rats were exposed to either 80% +/- 2% oxygen to postnatal day P11 and then room air until P18 (ROP) or room air for the entire duration (controls). Retinal structure was examined under the light microscope and following postembedding immunocytochemistry in central, midperipheral, and peripheral regions. Müller cells were evaluated immunocytochemically with glial fibrillary acidic protein. The extent of vascularization was established histologically. ROP caused significant thinning of the inner cellular and plexiform layers, which became more pronounced in the peripheral inner nuclear layer of ROP animals (11.3% loss vs. 25.4% loss). Amacrine cell amino acid levels were particularly vulnerable in the peripheral retina; bipolar cells showed similar but less prominent changes. Müller cells had elevated glutamine levels and were most gliotic in the periphery. The vasculature extended to peripheral retinal regions at P18 in controls but not in ROP rats. The most striking pattern of change was evident in the midperipheral "transition zone" of ROP animals. Areas close to blood vessels showed neurochemical properties that were similar to those of the central retina, indicating a local protective effect of the inner retinal blood supply. We find that ROP produces complex vascular, neural, and glial changes that relate to the proximity of inner retinal blood vessels.

Expression pattern and cellular sources of chemokines in primary central nervous system lymphoma

The expression pattern of a subset of chemokines and their corresponding receptors was investigated in primary central nervous system lymphomas (PCNSL). The tumor cells consistently expressed CXCR4, CXCL12, CXCR5, and CXCL13, both at mRNA and protein levels. Cerebral endothelial cells were positive for CXCL12 and CXCL13, while reactive astrocytes and microglial cells expressed CXCL12, CCR5, and CCR6. Inflammatory T cells in PCNSL were characterized by CCR5 and CCR6 positivity. Taken together, our data indicate a cell type-specific repertoire of chemokine and chemokine receptor expression in PCNSL suggesting that chemokine-mediated interactions facilitate crossing of the blood-brain barrier as well as intracerebral dissemination of PCNSL cells. In addition, chemokines expressed by tumor cells may contribute to induction of reactive glial changes and influence the composition of inflammatory infiltrates in PCNSL. Therefore, cell type specific expression of distinct chemokine profiles likely plays a role in the pathogenesis of PCNSL and may contribute to their characteristic histological appearance.

In utero topographic analysis of astrocytes and neuronal cells in the spinal cord of mutant mice with myelomeningocele

Myelomeningocele (MMC) is the most severe form of spina bifida causing severe neurological deficits. Injury to the placode has been attributed to in utero aggression. In this study, glial and neuronal cell changes in both number and topography in mice with MMC were investigated during gestation. The curly tail/loop-tail mice model of MMC was used, and fetuses were harvested using caesarean surgery at Days 14.5, 16.5, and 18.5 (full gestation at 19 days). Immunohistochemical analyses of the MMC placodes and the normal spinal cords from the control group were performed using anti-glial fibrillary acidic protein (astrocytes) and mouse anti-neuronal nuclear (neurons) antibodies. Light microscopy was used along with computer-assisted morphometric evaluation. Progressive increases in astrocytes in the spinal cord of all mouse fetuses were found between Days 14.5 and 18.5 of gestation. This increase was significantly higher in the placodes of mice with MMC than in those of normal mice, particularly in the posterior region. Neuronal labeling at Day 14.5 of gestation was similar between mice with MMC and control mice. At Day 16.5 of gestation there was a deterioration of neural tissue in MMC fetuses, mainly in the posterior region, progressing until the end of gestation with a marked loss of neurons in the entire MMC placode. This study delineated the quantitative changes in astrocytes and neurons associated with MMC development during the late stages of gestation. The detailed topographic analysis of the MMC defines the timing of the intrauterine insult and how the placode lesions progress. This study supports the current concept of placode protection through in utero surgery for fetuses with MMC.

What causes the hippocampal volume decrease in depression?

Even though in vivo imaging studies document significant reductions of hippocampal volume in depressed patients, the exact underlying cellular mechanisms are unclear. Since stressful life events are associated with an increased risk of developing depression, preclinical studies in which animals are exposed to chronic stress have been used to understand the hippocampal shrinkage in depressed patients. Based on morphometrical studies in these models, parameters like dendritic retraction, suppressed adult neurogenesis and neuronal death, all due to elevated levels of glucocorticoids, have been suggested as major causative factors in hippocampal shrinkage. However, histopathological studies examining hippocampi of depressed individuals have so far failed to confirm either a massive neuronal loss or a suppression of dentate neurogenesis, an event that is notably very rare in adult or elderly humans. In fact, many of the structural changes and the volume reduction appear to be reversible. Clearly, more histopathological studies are needed; especially ones that (a) employ stereological quantification, (b) focus on specific cellular elements and populations, and (c) are performed in nonmedicated depressed patients. We conclude that mainly other factors, like alterations in the somatodendritic, axonal, and synaptic components and putative glial changes are most likely to explain the hippocampal shrinkage in depression, while shifts in fluid balance or changes in the extracellular space cannot be excluded either.

Thalamic hypometabolism on 18FDG-positron emission tomography in medial temporal lobe epilepsy

Objectives: Degree of hypometabolism in the thalamus on 18Fluorodeoxyglucose-positron emission tomography (FDG-PET) was compared with those of medial and lateral temporal lobes in patients with medial temporal lobe epilepsy (mTLE), and its relationship with post-operative seizure outcomes was investigated.Methods: Twenty-six patients with mTLE who underwent anterior temporal lobectomy were included. Post-operatively, 13 patients became completely seizure-free and 13 showed residual seizure, regardless of frequency (five patients became almost seizure-free, six had rare seizures and two showed significant improvements). Degrees of hypometabolism in bilateral thalamus, ipsilateral medial and lateral temporal lobes were evaluated visually and semi-quantitatively by determining the asymmetry index (AI), a value indicating 100 × (ipsilateral - contralateral)/[1/2 × (ipsilateral + contralateral)] and the region-to-cerebral hemisphere ratio (R/C ratio) being the ratio between averaged counts in each area and those in the cerebral hemisphere of the same side.Results: Hypometabolism in the medial temporal lobe was visually observed in all patients. Hypometabolism in the lateral temporal lobe was observed in 20 patients and was semi-quantitatively more prominent than that of the medial temporal lobe. Pathologically, hippocampal sclerosis and prominent astrogliosis of the lateral temporal lobe were present in all cases. However, while thalamic hypometabolism was visually observed in nine patients (in the ipsilateral side of four cases, contralateral side of three and on both sides of two), no significant thalamic hypometabolism was semi-quantitatively observed. No significant differences in metabolic rate in any area except for the lateral temporal lobe between seizure-free patients and residual seizure patients were seen semi-quantitatively.Discussion: Data indicated that metabolism in the lateral temporal lobe of patients with mTLE significantly decreased and revealed pathologic glial changes. Thalamic hypometabolism was quite mild and did not correlate with post-operative seizure outcome.

Canine cognitive dysfunction and the cerebellum: Acetylcholinesterase reduction, neuronal and glial changes

The specific functional and pathological alterations observed in Alzheimer's disease are less severe in the cerebellum than in other brain areas, particularly the entorhinal cortex and hippocampus. Since dense core amyloid-beta plaque formation has been associated with an acetylcholinesterase heterogeneous nucleator action, we examined if an acetylcholinesterase imbalance was involved in cerebellum plaque deposition. By using the canine counterpart of senile dementia of the Alzheimer's type, a promising model of human brain aging and early phases of Alzheimer's disease, we investigated how cerebellar pathology and acetylcholinesterase density could be related with cognitive dysfunction. As in Alzheimer's disease, the late affectation of the cerebellum was evidenced by its lack of amyloid-beta plaque and the presence of diffuse deposition throughout all cortical grey matter layers. The highest acetylcholinesterase optic density corresponded to cerebellar islands of the granular layer and was predominantly associated with synaptic glomeruli and the somata of Golgi cells. Its reduction correlated with aging and loss of granule cells, whereas cognitive deficit only correlated with loss of Purkinje cells. The observed Bergmann glia alterations may correspond to a reactive response to the loss and damage of the Purkinje cells, their specific neuronal partner. Regarding the role of acetylcholinesterase mediation in amyloid-beta deposition, our data argue against an interaction between these two proteins because acetylcholinesterase reduction correlates with aging but not with cognitive deficit. Finally, our data support the use of companion dogs of all breeds to study aging and early phases of Alzheimer's disease.

Responses of reactive astrocytes containing S100β protein and fibroblast growth factor‐2 in the border and in the adjacent preserved tissue after a contusion injury of the spinal cord in rats: implications for wound repair and neuroregeneration

This paper demonstrates glial reaction and changes in the S100beta protein and basic fibroblast growth factor (bFGF, FGF-2) in the border and in the adjacent preserved tissue of the rat spinal cord after a contusion. In view of the expression of FGF-2 and S100beta in reactive glial cells and their ability to promote gliogenesis and neuronal trophism, the molecules have been considered to participate in the wound repair and regenerative events after nervous tissue injury. Adult rats were submitted to a moderate spinal cord (10th thoracic level) contusion induced by a New York University Impactor by dropping a 10 g rod from a distance of 25 mm onto the dorsal surface of the exposed dura spinal cord. Impactor curves and parameters were used to monitor the severity of the trauma. Control rats were submitted to sham operation. The motor behavioral spontaneous recovery was demonstrated by means of a BBB test and the combining behavior score up to 3 weeks after injury. Animals were killed 72 hours, 2, and 3 weeks after surgery and spinal cords were processed for immunohistochemistry to show glial fibrillary acidic protein positive astrocytes and OX-42-positive microglia/macrophages as well as changes in the S100beta and FGF-2 in the border and in the adjacent preserved tissue of the lesioned cords. The changes in the immunoreaction products were quantified by means of morphometric/microdensitometric image analysis, and the cell type expressing S100beta and FGF-2 was analyzed by means of two-color immunofluorescence procedures. Massive increases of S100beta and FGF-2 were found in reactive astrocytes, not in reactive microglia, in the border and in the white and gray matters of adjacent preserved tissue of the contused spinal cord in the periods studied. The results are discussed in view of possible paracrine trophic actions of the reactive astrocytes, mediated by S100beta and FGF-2, triggering wound repair events in the border of the trauma, and also leading to neurotrophism and neuronal plasticity in the adjacent regions. These cellular and molecular responses may interfere with the pattern of behavioral recovery after a contusion injury of the spinal cord.