Changes In Brain Morphology Research Articles

Brain changes in Kallmann syndrome.

Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome-related brain changes with conventional and novel quantitative MR imaging analyses. Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9-55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value=800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library. Corpus callosum partial agenesis, multiple sclerosis-like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus. This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

Endocranial morphology of Palaeocene Plesiadapis tricuspidens and evolution of the early primate brain.

Expansion of the brain is a key feature of primate evolution. The fossil record, although incomplete, allows a partial reconstruction of changes in primate brain size and morphology through time. Palaeogene plesiadapoids, closest relatives of Euprimates (or crown-group primates), are crucial for understanding early evolution of the primate brain. However, brain morphology of this group remains poorly documented, and major questions remain regarding the initial phase of euprimate brain evolution. Micro-CT investigation of the endocranial morphology of Plesiadapis tricuspidens from the Late Palaeocene of Europe--the most complete plesiadapoid cranium known--shows that plesiadapoids retained a very small and simple brain. Plesiadapis has midbrain exposure, and minimal encephalization and neocorticalization, making it comparable with that of stem rodents and lagomorphs. However, Plesiadapis shares a domed neocortex and downwardly shifted olfactory-bulb axis with Euprimates. If accepted phylogenetic relationships are correct, then this implies that the euprimate brain underwent drastic reorganization during the Palaeocene, and some changes in brain structure preceded brain size increase and neocortex expansion during evolution of the primate brain.

Juggling revisited — A voxel–based morphometry study with expert jugglers

Juggling is a highly interesting tool to investigate neuroplasticity associated with motor-learning. Several brain-imaging studies have reported changes in regional brain morphology in visual association cortices in individuals learning how to juggle a three-ball cascade. However, to our knowledge there are no studies that investigated expert jugglers, looking for specific features in regional brain morphology related to this highly specialized skill.Using T1-weighted images and voxel-based morphometry we investigated in a cross-sectional study design 16 expert jugglers, able to juggle at least five balls and an age- and gender-matched group of non-jugglers. We hypothesized that expert jugglers would show higher gray matter density in regions involved in visual motion perception and eye-hand coordination. Images were pre-processed and analyzed using SPM8. Age was included in the analyses as covariate of no interest.As compared to controls jugglers displayed several clusters of higher, regional gray matter density in the occipital and parietal lobes including the secondary visual cortex, the hMT+/V5 area bilaterally and the intraparietal sulcus bilaterally. Within the jugglers group we also found a correlation between performance and regional gray matter density in the right hMT+/V5 area.Our study provides evidence that expert jugglers show increased gray matter density in brain regions involved in visual motion perception and eye–hand coordination, i.e. brain areas that have previously been shown to undergo dynamic changes in terms of gray matter increases in subjects learning a basic three-ball cascade. The extent to which transient increases in beginners and the differences in experts and non-experts are based on the same neurobiological correlates remains to be fully elucidated.

COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans

Genetic variations in catechol-O-methyltransferase (COMT) that modulate cortical dopamine have been associated with pleiotropic behavioral effects in humans and mice. Recent data suggest that some of these effects may vary among sexes. However, the specific brain substrates underlying COMT sexual dimorphisms remain unknown. Here, we report that genetically driven reduction in COMT enzyme activity increased cortical thickness in the prefrontal cortex (PFC) and postero-parieto-temporal cortex of male, but not female adult mice and humans. Dichotomous changes in PFC cytoarchitecture were also observed: reduced COMT increased a measure of neuronal density in males, while reducing it in female mice. Consistent with the neuroanatomical findings, COMT-dependent sex-specific morphological brain changes were paralleled by divergent effects on PFC-dependent working memory in both mice and humans. These findings emphasize a specific sex-gene interaction that can modulate brain morphological substrates with influence on behavioral outcomes in healthy subjects and, potentially, in neuropsychiatric populations.

Lycium barbarum Polysaccharide Prevents Focal Cerebral Ischemic Injury by Inhibiting Neuronal Apoptosis in Mice

Aims of the StudyTo investigate the neuroprotective effect of Lycium barbarum polysaccharide (LBP) on focal cerebral ischemic injury in mice and to explore its possible mechanism.Materials and MethodsMale ICR mice were used to make the model of middle cerebral artery occlusion (MCAO) after intragastric administration with LBP (10, 20 and 40 mg/kg) and Nimodipine (0.4 mg/kg) for seven successive days. After 24 h of reperfusion, neurological scores were estimated and infarct volumes were measured by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Morphological changes in ischemic brains were performed for hematoxylin-eosin (HE) staining. The number of apoptotic neurons was detected by TUNEL staining. The Bax, Bcl-2 protein expression and CytC, Caspase-3, -9 and cleaved PARP-1 activation were investigated by immunofluorescence and western-blot analysis.ResultsLBP (10, 20 and 40 mg/kg) treatment groups significantly reduced infract volume and neurological deficit scores. LBP also relieved neuronal morphological damage and attenuated the neuronal apoptosis. LBP at the dose of 40 mg/kg significantly suppressed overexpression of Bax, CytC, Caspase-3, -9 and cleaved PARP-1, and inhibited the reduction of Bcl-2 expression.ConclusionsBased on these findings we propose that LBP protects against focal cerebral ischemic injury by attenuating the mitochondrial apoptosis pathway.

Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes.

Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex.

Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes.

Histological evaluation of the prefrontal cortex of infantile Wistar rats exposed to nicotine during the embryonic period

Exposure to nicotine in utero is neuroteratogenic, predisposing the developing brain to cell injury and many forms of neurological and neurobehavioural problems that persist after birth. The current study examined some of the histological effects of prenatal nicotine exposure on the prefrontal cortex of infantile rats. Primiparous Wistar rats were mated, and pregnancy was confirmed. A daily dose of 0.03 mg/kg of nicotine was administered intra-peritoneally to each treated rat for five consecutive days during their first two weeks of gestation. The rate of development and maturation of brain cells was reduced, as well as a reduction in the population of cells, though no apparent reduction of brain weight or morphological changes was noticed.Keywords: prenatal nicotine, prefrontal cortex, infantile rats

Brain functional connectivity and morphology changes in medication-overuse headache: Clue for dependence-related processes?

Several imaging studies have identified localized anatomical and functional brain changes in medication-overuse headache (MOH). The objective of this article is to evaluate whole-brain functional connectivity at rest together with voxel-based morphometry in MOH patients, in comparison with episodic migraine (EM) patients and healthy controls (HCs). Anatomical MRI and resting-state functional MRI scans were obtained in MOH patients (n = 17 and 9, respectively), EM patients (n = 18 and 15, respectively) and HCs (n = 17 and 17). SPM8 was used to analyze voxel-based morphometry and seed (left precuneus) to voxel connectivity data in the whole brain. Functional connectivity at rest was altered in MOH patients. Connectivity was decreased between precuneus and regions of the default-mode network (frontal and parietal cortices), but increased between precuneus and hippocampal/temporal areas. These functional modifications were not accompanied by significant gross morphological changes. Furthermore, connectivity between precuneus and frontal areas in MOH was negatively correlated with migraine duration and positively correlated with self-evaluation of medication dependence. Gray matter volumes of frontal regions, precuneus and hippocampus were also negatively related to migraine duration. Functional connectivity within the default-mode network appeared to predict anxiety scores of MOH patients while gray matter volumes in this network predicted their depression scores. Our data suggest that MOH is associated with functional alterations within intrinsic brain networks rather than with macrostructural changes. They also support the view that dependence-related processes might play a prominent role in its development and maintenance.

Atypical sulcal anatomy in young children with autism spectrum disorder.

Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory that could be part of the primary pathology.

Gray matter alterations in chronic pain: A network-oriented meta-analytic approach.

Several studies have attempted to characterize morphological brain changes due to chronic pain. Although it has repeatedly been suggested that longstanding pain induces gray matter modifications, there is still some controversy surrounding the direction of the change (increase or decrease in gray matter) and the role of psychological and psychiatric comorbidities. In this study, we propose a novel, network-oriented, meta-analytic approach to characterize morphological changes in chronic pain. We used network decomposition to investigate whether different kinds of chronic pain are associated with a common or specific set of altered networks. Representational similarity techniques, network decomposition and model-based clustering were employed: i) to verify the presence of a core set of brain areas commonly modified by chronic pain; ii) to investigate the involvement of these areas in a large-scale network perspective; iii) to study the relationship between altered networks and; iv) to find out whether chronic pain targets clusters of areas. Our results showed that chronic pain causes both core and pathology-specific gray matter alterations in large-scale networks. Common alterations were observed in the prefrontal regions, in the anterior insula, cingulate cortex, basal ganglia, thalamus, periaqueductal gray, post- and pre-central gyri and inferior parietal lobule. We observed that the salience and attentional networks were targeted in a very similar way by different chronic pain pathologies. Conversely, alterations in the sensorimotor and attention circuits were differentially targeted by chronic pain pathologies. Moreover, model-based clustering revealed that chronic pain, in line with some neurodegenerative diseases, selectively targets some large-scale brain networks. Altogether these findings indicate that chronic pain can be better conceived and studied in a network perspective.

Post-adolescent developmental changes in cortical complexity.

BackgroundPost-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval.MethodsMagnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 14 young adults (mean age 24.24 ± 2.76, 7 women) for measures of brain complexity (fractal dimension - FD), grey matter (GM) volume and surface-area of cortical ribbon. FD was calculated using box-counting and Minkowski-Bouligand methods; FD and GM volume were measured for the whole brain, each hemisphere and lobes: frontal, occipital, parietal and temporal.ResultsThe results show that the adults have a lower cortical complexity than the adolescents, which was significant for whole brain, left and right hemisphere, frontal and parietal lobes for both genders; and only for males in left temporal lobe. The GM volume was smaller in men than in boys for almost all measurements, and smaller in women than in girls just for right parietal lobe. A significant Pearson correlation was found between FD and GM volume for whole brain and each hemisphere in both genders. The decrease of the GM surface-area was significant in post-adolescence for males, not for females.ConclusionsDuring post-adolescence there are common changes in cortical complexity in the same regions for both genders, but there are also gender specific changes in some cortical areas. The sex differences from different cortical measurements (FD, GM volume and surface-area of cortical ribbon) could suggest a maturation delay in specific brain regions for each gender in relation to the other and might be explained through the functional role of the corresponding regions reflected in gender difference of developed abilities.

Sports and brain morphology – A voxel-based morphometry study with endurance athletes and martial artists

Physical exercises and motor skill learning have been shown to induce changes in regional brain morphology, this has been demonstrated for various activities and tasks. Also individuals with special skills show differences in regional brain morphology. This has been indicated for professional musicians, London taxi drivers, as well as for athletes like dancers, golfers and judokas. However little is known about whether sports with different metabolic profiles (aerobic vs. anaerobic) are associated with different patterns of altered brain morphology.In this cross-sectional study we investigated two groups of high-performance athletes, one group performing sports that are thought to be mainly aerobic, and one group performing sports known to have intermittent phases of anaerobic metabolism. Using high-resolution structural imaging and voxel-based morphometry (VBM), we investigated a group of 26 male athletes consisting of 13 martial artists and 13 endurance athletes as well as a group of non-exercising men (n=13).VBM analyses revealed higher gray matter (GM) volumes in the supplementary motor area/dorsal premotor cortex (BA 6) in both athlete groups as compared to the control group. In addition, endurance athletes showed significantly higher GM volume in the medial temporal lobe (MTL), specifically in the hippocampus and parahippocampal gyrus, which was not seen in the martial arts group.Our data suggest that high-performance sports are associated with changes in regional brain morphology in areas implicated in motor planning and motor learning. In addition high-level endurance sports seem to affect MTL structures, areas that have previously been shown to be modulated by aerobic exercise.

Cortical thickness, cortical and subcortical volume, and white matter integrity in patients with their first episode of major depression

BackgroundThe uncertainty over the true morphological changes in brains with major depressive disorder (MDD) underlines the necessity of comprehensive studies with multimodal structural brain imaging analyses. This study aimed to evaluate the differences in cortical thickness, cortical and subcortical volume, and white matter integrity between first episode, medication-naïve MDD patients and healthy controls. MethodsSubjects with their first episode of MDD whose illness duration had not exceeded 6 months (n=20) were enrolled in this study and were compared to age-, sex-, and education level-matched healthy controls (n=22). All participants were subjected to T1-weighted structural magnetic resonance imaging (MRI). We used an automated procedure of FreeSurfer and Tract-based spatial statistics (TBSS) to analyze differences in cortical thickness, cortical and subcortical volume, and white matter integrity between two groups. ResultsThe patients with first episode MDD exhibited significantly reduced cortical volume in the caudal anterior cingulate gyrus (P<0.0015) compared to healthy controls. We also observed altered white matter integrity in the body of the corpus callosum (P<0.01), reduced cortical volume of the caudal middle frontal gyrus and medial orbitofrontal gyrus, and enlarged hippocampal volume in the first episode MDD patients. LimitationsWe relied on a relatively small sample size and cortical volume reduction in several brain regions was not replicated in the analysis of cortical thickness. ConclusionsUsing multimodal imaging analyses on medication-naïve first episode MDD patients, we demonstrated fundamental structural alteration of brain gray and white matter, such as reduced cortical volume of the caudal ACC and white matter integrity in the body of the corpus callosum.

Psychosis effect on hippocampal reduction in schizophrenia

In schizophrenia, disruption of the neurodevelopmental processes may lead to brain changes and subsequent clinical manifestations of the illness. Reports of the progressive nature of these morphological brain changes raise questions about their causes. The possible toxic effects of repeated stressful psychotic episodes may contribute to the disease progression. To analyze the influence of illness duration and previous psychotic episodes on hippocampal gray matter volume (GMV) in schizophrenia. We performed an analysis of hippocampal GMV correlations with illness duration, number of previous psychotic episodes, and age in 24 schizophrenia patients and 24 matched healthy controls. We found a cluster of GMV voxels in the left hippocampal tail that negatively correlated with the number of previous psychotic episodes, independent from the effect of age. On the other hand we found no effect of illness duration independent of age on the hippocampal GMV. Finally, we found a cluster of significant group-by-age interaction in the left hippocampal head. We found an additive adverse effect of psychotic episodes on hippocampal morphology in schizophrenia. Our findings support toxicity of psychosis concept, together with etiological heterogeneity of brain changes in schizophrenia.

RESTING FUNCTIONAL CONNECTIVITY REVEALS RESIDUAL FUNCTIONAL ACTIVITY IN ALZHEIMER'S DISEASE

ObjectiveFunctional MRI (fMRI) has great potential for unravelling mechanisms of functional decline in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI), but task–fMRI studies have produced conflicting results, partly due...

Neurobiology of ADHD From Childhood to Adulthood

Objective: To review the pattern of morphological and functional brain changes in both children and adults with ADHD that emerges from the recent literature. In addition, the task of the present review is to explore how to understand the nature of the brain changes. Methods: Literature review. Results: Neuroimaging studies provide a multitude of information that currently allows us to expand the notions of ADHD neurobiology beyond its traditional understanding as a manifestation of frontostriatal dysfunction. They point to disorders of several other areas of the brain, particularly the anterior cingulum, the dorsolateral as well as ventrolateral prefrontal cortex, the orbitofrontal cortex, the superior parietal regions, the caudate nucleus, the thalamus, the amygdala and the cerebellum. Imaging studies point to the persistence of changes in both brain structure and function into adulthood, although there might be a tendency for improvement of caudate nucleus pathology. Changes in neuronal (dendritic) plasticity, which are under the modulatory influence of the dopaminergic system, may be in the background of disorders of brain morphology and anatomical connectivity with subsequent brain dysfunction. Growing evidence suggest that methylphenidate treatment can lead to improvement of brain changes seen in neuroimaging by its positive effect on neuroplasticity. Conclusion: Changes in neuronal plasticity may be behind persisting brain changes in ADHD. Current treatment approaches seem to improve these neuroplastic processes, and, therefore, may have a positive effect on the neuropathology of ADHD.

Ablation of RIC8A Function in Mouse Neurons Leads to a Severe Neuromuscular Phenotype and Postnatal Death

Resistance to inhibitors of cholinesterase 8 (RIC8) is a guanine nucleotide exchange factor required for the intracellular regulation of G protein signalling. RIC8 activates different Gα subunits via non-canonical pathway, thereby amplifying and prolonging the G protein mediated signal. In order to circumvent the embryonic lethality associated with the absence of RIC8A and to study its role in the nervous system, we constructed Ric8a conditional knockout mice using Cre/loxP technology. Introduction of a synapsin I promoter driven Cre transgenic mouse strain (SynCre) into the floxed Ric8a (Ric8a F/F) background ablated RIC8A function in most differentiated neuron populations. Mutant SynCre +/- Ric8 lacZ/F mice were born at expected Mendelian ratio, but they died in early postnatal age (P4-P6). The mutants exhibited major developmental defects, like growth retardation and muscular weakness, impaired coordination and balance, muscular spasms and abnormal heart beat. Histological analysis revealed that the deficiency of RIC8A in neurons caused skeletal muscle atrophy and heart muscle hypoplasia, in addition, the sinoatrial node was misplaced and its size reduced. However, we did not observe gross morphological changes in brains of SynCre +/- Ric8a lacZ/F mutants. Our results demonstrate that in mice the activity of RIC8A in neurons is essential for survival and its deficiency causes a severe neuromuscular phenotype.

The cyanobacterial amino acid β-N-methylamino-l-alanine perturbs the intermediary metabolism in neonatal rats

The neurotoxic amino acid β-N-methylamino-l-alanine (BMAA) is produced by most cyanobacteria. BMAA is considered as a potential health threat because of its putative role in neurodegenerative diseases. We have previously observed cognitive disturbances and morphological brain changes in adult rodents exposed to BMAA during the development. The aim of this study was to characterize changes of major intermediary metabolites in serum following neonatal exposure to BMAA using a non-targeted metabolomic approach. NMR spectroscopy was used to obtain serum metabolic profiles from neonatal rats exposed to BMAA (40, 150, 460mg/kg) or vehicle on postnatal days 9–10. Multivariate data analysis of binned NMR data indicated metabolic pattern differences between the different treatment groups. In particular five metabolites, d-glucose, lactate, 3-hydroxybutyrate, creatine and acetate, were changed in serum of BMAA-treated neonatal rats. These metabolites are associated with changes in energy metabolism and amino acid metabolism. Further statistical analysis disclosed that all the identified serum metabolites in the lowest dose group were significantly (p<0.05) decreased. The neonatal rat model used in this study is so far the only animal model that displays significant biochemical and behavioral effects after a low short-term dose of BMAA. The demonstrated perturbation of intermediary metabolism may contribute to BMAA-induced developmental changes that result in long-term effects on adult brain function.

Effects of ginkgo biloba extract on the expression of inducible nitric oxide synthase and glial fibrillary acidic protein after local cerebral ischemia/reperfusion in rats

Objective To explore the protective effect and mechanism of ginkgo biloba extract on brain tissue after local cerebral ischemia and reperfusion in rats.Methods Eighty male Sprague-Dawley rats were randomly divided into two groups:control group (group A,normal saline injected,n =40),and ginkgo biloba extract intervention group (group B,ginkgo biloba extract injected,n =40),which were then subdivided into 4 subgrouops:post-reperfusion 1,3,6 and 24 h groups,10 in each sub-group.The model of right middle cerebral artery occlusion (MCAO) and reperfusion was made.Pathological changes in brain morphology were observed by hematoxylin and eosin (HE) staining.Immunohitochemistry was used to detect the inducible nitric oxide synthase (iNOS) changes.The expression of glial fibrillary acidic protein (GFAP) was examined by using enzyme linked immunosorbent assay (ELISA).Results (1) Necrosis,apoptosis and cytoplasmic vacuolatin of nerve cells were observed in group A,neuronal shape was difficult to be identified,and most of the cell structure disappeared.However,the injury was relieved at the same time points in group B as compared with that in group A; (2) Immunohitochemical results showed that there were a few iNOS expression positive cells 1 h after reperfusion,iNOS expression positive cells were obviously increased at 3 h after referfusion,and nucler translocation appeared.Analysis by Image-pro plus 5.0 showed that iNOS expression levels in group B (1851.38 ±242.12,2005.41 ± 290.52,2625.28 ±385.21,3142.5 ±425.72 respectively at 1,3,6 and 24 h) were significantly lower than those in group A (1950.25 ± 298.26,2232.45 ± 305.28,3251.22 ± 425.26,3965.36 ± 521.62 respectively at 1,3,6and 24 h) (P ＜ 0.05) ; (3) ELISA results showed that serum GFAP levels were increased after ischemiareperfusion,and those in group B [(275.29 ± 112.72),(308.72 ±124.11),(372.56 ± 185.62),(452.12 ± 145.26) ng/L respectively at 1,3,6 and 24 h] were significantly lower than those in group A [(437.17 ± 152.26),(490.27 ± 198.37),(583.45 ± 201.42),(656.26 ± 256.36) ng/L respectively at 1,3,6 and 24 h] (P ＜ 0.05).Conclusion iNOS and GFAP were significantly increased after the cerebral ischemia-reperfusion in rats.ginkgo biloba extract can significantly reduce the cerebral injury by down-regulating the expression of iNOS and GFAP,suggesting the protective effects of ginkgo biloba extract on the ischemic cerebral tissues. Key words: Ginkgo biloba extract; Ischemia/reperfusion injury; Apoptosis; Inducible nitric oxide synthase