Neonatal valproic acid exposure produces altered gyrification related to increased parvalbumin-immunopositive neuron density with thickened sulcal floors.

Valproic acid (VPA) treatment is associated with autism spectrum disorder in humans, and ferrets can be used as a model to test this; so far, it is not known whether ferrets react to developmental VPA exposure with gyrencephalic abnormalities. The current study characterized gyrification abnormalities in ferrets following VPA exposure during neonatal periods, corresponding to the late stage of cortical neurogenesis as well as the early stage of sulcogyrogenesis. Ferret pups received intraperitoneal VPA injections (200 µg/g of body weight) on postnatal days (PD) 6 and 7. BrdU was administered simultaneously at the last VPA injection. Ex vivo MRI-based morphometry demonstrated significantly lower gyrification index (GI) throughout the cortex in VPA-treated ferrets (1.265 ± 0.027) than in control ferrets (1.327 ± 0.018) on PD 20, when primary sulcogyrogenesis is complete. VPA-treated ferrets showed significantly smaller sulcal-GIs in the rostral suprasylvian sulcus and splenial sulcus but a larger lateral sulcus surface area than control ferrets. The floor cortex of the inner stratum of both the rostral suprasylvian and splenial sulci and the outer stratum of the lateral sulcus showed a relatively prominent expansion. Parvalbumin-positive neuron density was significantly greater in the expanded cortical strata of sulcal floors in VPA-treated ferrets, regardless of the BrdU-labeled status. Thus, VPA exposure during the late stage of cortical neurogenesis may alter gyrification, primarily in the frontal and parietotemporal cortical divisions. Altered gyrification may thicken the outer or inner stratum of the cerebral cortex by increasing parvalbumin-positive neuron density.

The Effect of Chronic Ethanol Exposure and Thiamine Deficiency on Myelin-related Genes in the Cortex and the Cerebellum.

BACKGROUND: Long-term alcohol consumption has been linked to structural and functional brain abnormalities. Furthermore, with persistent exposure to ethanol (EtOH), nutrient deficiencies often develop. Thiamine deficiency is a key contributor to alcohol-related brain damage and is suspected to contribute to white matter pathology. The expression of genes encoding myelin proteins in several cortical brain regions is altered with EtOH exposure. However, there is limited research regarding the impact of thiamine deficiency on myelin dysfunction. METHODS: A rat model was used to assess the impact of moderate chronic EtOH exposure (CET; 20% EtOH in drinking water for 1 or 6 months), pyrithiamine-induced thiamine deficiency treatment (PTD), both conditions combined (CET-PTD), or CET with thiamine injections (CET + T) on myelin-related gene expression (Olig1, Olig2, MBP, MAG, and MOG) in the frontal and parietal cortices and the cerebellum. RESULTS: The CET-PTD treatments caused the greatest suppression in myelin-related genes in the cortex. Specifically, the parietal cortex was the region that was most susceptible to PTD-CET-induced alterations in myelin-related genes. In addition, PTD treatment, with and without CET, caused minor fluctuations in the expression of several myelin-related genes in the frontal cortex. In contrast, CET alone and PTD alone suppressed several myelin-related genes in the cerebellum. Regardless of the region, there was significant recovery of myelin-related genes with extended abstinence and/or thiamine restoration. CONCLUSION: Moderate chronic EtOH alone had a minor effect on the suppression of myelin-related genes in the cortex; however, when combined with thiamine deficiency, the reduction was amplified. There was a suppression of myelin-related genes following long-term EtOH and thiamine deficiency in the cerebellum. However, the suppression in the myelin-related genes mostly occurred 24 h after EtOH removal or following thiamine restoration; within 3 weeks of abstinence or thiamine recovery, gene expression rebounded.

Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.

Dystrophic neurites and activated microglia are one of the main neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 fatty acids has been associated with reduced risk and lessened AD pathology, it still remains elusive whether such a treatment could affect dystrophic neurites (DNs) formation and microglia/macrophage behavior in the early phase of disease. We analyzed the effects of short-term (3 weeks) fish oil supplementation on DNs formation, tau hyperphosphorylation, Amyloid-beta peptide 1-42 (Aß42) levels and microglial/macrophage response to AD pathology in the parietal cortex of 4-month-old 5xFAD mice, a mouse model of AD. The present study shows for the first time that short-term FO supplementation applied in presymptomatic stage of AD, alters the behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier significantly suppresses DNs formation through the reduction of both Aß content and tau hyperphosphorylation. Moreover, the short-term FO treatment neither suppresses inflammation nor enhances phagocytic properties of microglia/macrophages in the response to Aß pathology, the effects most commonly attributed to the fish oil supplementation. Our findings suggest that fish oil consumption may play an important role in modulating microglial/macrophage response and ameliorating the AD pathology in presymptomatic stage of Alzheimer's disease.

The role of the deeper layers of the superior colliculus in attentional modulations of prepulse inhibition.

Prepulse inhibition (PPI) is the suppression of the startle reflex, when a weaker non-startling sensory stimulus (the prepulse) precedes the intense startling stimulus. Although the basic PPI neural circuitry resides in the brainstem, PPI can be enhanced by selective attention to the prepulse, indicating that this sensorimotor-gating process is influenced by higher-order perceptual/cognitive processes. Along with the auditory cortex, the brain structures involved in attentional modulations of PPI include both the lateral nucleus of the amygdala (LA), which contributes to the fear-conditioning modulation, and the posterior parietal cortex (PPC), which contributes to the spatially attentional modulation. The deeper layers of the superior colliculus (DpSC), which has been suggested as a midbrain component in the PPI circuitry, receive descending axonal projections from some forebrain structures associated with auditory perception, emotional conditioning, or spatial attention. This study was to examine whether the DpSC are also involved in attentional modulations of PPI in rats. The results showed that both fear conditioning of a prepulse sound and precedence-effect-induced perceptual separation between the conditioned prepulse and a noise masker facilitated selective attention to the prepulse and consequently enhanced PPI. Reversibly blocking glutamate receptors in the DpSC with 2-mM kynurenic acid eliminated both the conditioning-induced and the perceptual-separation-induced PPI enhancements. However, the baseline magnitudes of startle and PPI were not affected. The results suggest that the DpSC play a role in mediating the attentional enhancements of PPI, probably through both receiving top-down signals from certain forebrain structures and modulating the midbrain representations of prepulse signals.

A Combination of Essential Fatty Acids, Panax Ginseng Extract, and Green Tea Catechins Modifies Brain fMRI Signals in Healthy Older Adults.

OBJECTIVES: To assess the effects of a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides on cognition and brain functioning in healthy older adults. DESIGN: Double-blind, placebo-controlled, crossover design randomized controlled trial with 26-day intervention phases and a 30-day washout period. SETTING: The Institute for Dementia Research and Prevention at the Pennington Biomedical Research Center. PARTICIPANTS: Ten independently-living, cognitively-healthy older adults (mean age: 67.3 + 2.01 years). INTERVENTION: Daily consumption of an investigational product (trade name "Cerbella TM") consisting of an emulsified liquid combination of standardized fish oil, panax ginseng extract, and green tea catechins in a flavored base of lecithin phospholipids optimized to maximize bioavailability of the active ingredients. MEASUREMENTS: Before and after supplementation with the investigational product or placebo, participants completed cognitive tests including the Mini Mental State Exam (MMSE), Stroop test, Digit Symbol Substitution Test (DSST), and Immediate and Delayed Recall tests, as well as functional magnetic resonance imaging (fMRI) during a standard cognitive task switching paradigm. RESULTS: Performance on the MMSE, Stroop test, and DSST increased significantly over one month of supplementation with the investigational product (one-sample t tests, p<.05) although differences between these changes and corresponding changes during supplementation with placebo were not significant (two-sample t tests, p>.05). During supplementation with the investigational product, brain activation during task performance increased significantly more than during supplementation with placebo in brain regions known to be activated by this task (anterior and posterior cingulate cortex). Functional connectivity during task execution between task regions (middle frontal gyrus and anterior cingulate cortex) increased significantly during supplementation with the investigational product, relative to placebo. Functional connectivity during rest between task regions (precentral gyrus and middle frontal gyrus) and default mode network regions (medial frontal gyrus and precuneus) decreased during supplementation with the investigational product relative to placebo, suggesting greater segregation of task and rest related brain activity. CONCLUSION: One-month supplementation with a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides was associated with suggestive changes in cognitive functioning as well as modification of brain activation and brain functional connectivity in cognitively healthy older adults.

Enhanced neural activation with blueberry supplementation in mild cognitive impairment.

OBJECTIVES: Preclinical studies have shown that blueberry supplementation can improve cognitive performance and neural function in aged animals and have identified associations between anthocyanins and such benefits. Preliminary human trials also suggest cognitive improvement in older adults, although direct evidence of enhancement of brain function has not been demonstrated. In this study, we investigated the effect of blueberry supplementation on regional brain activation in older adults at risk for dementia. METHODS: In a randomized, double-blind, placebo-controlled trial we performed pre- and post-intervention functional magnetic resonance imaging during a working memory (WM) task to assess the effect of blueberry supplementation on blood oxygen level-dependent (BOLD) signal in older adults with mild cognitive impairment, a risk condition for dementia. RESULTS: Following daily supplementation for 16 weeks, blueberry-treated participants exhibited increased BOLD activation in the left pre-central gyrus, left middle frontal gyrus, and left inferior parietal lobe during WM load conditions (corrected P < 0.01). There was no clear indication of WM enhancement associated with blueberry supplementation. Diet records indicated no between-group difference in anthocyanin consumption external to the intervention. DISCUSSION: These data demonstrate, for the first time, enhanced neural response during WM challenge in blueberry-treated older adults with cognitive decline and are consistent with prior trials showing neurocognitive benefit with blueberry supplementation in this at-risk population.

Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine.

Our previous studies have raised the possibility that altered blood glucose levels may influence and/or be predictive of methamphetamine (METH) neurotoxicity. This study evaluated the effects of exogenous glucose and corticosterone (CORT) pretreatment alone or in combination with METH on blood glucose levels and the neural and vascular toxicity produced. METH exposure consisted of four sequential injections of 5, 7.5, 10, and 10 mg/kg (2 h between injections) D-METH. The three groups given METH in combination with saline, glucose (METH+Glucose), or CORT (METH+CORT) had significantly higher glucose levels compared to the corresponding treatment groups without METH except at 3 h after the last injection. At this last time point, the METH and METH+Glucose groups had lower levels than the non-METH groups, while the METH+CORT group did not. CORT alone or glucose alone did not significantly increase blood glucose. Mortality rates for the METH+CORT (40%) and METH+Glucose (44%) groups were substantially higher than the METH (< 10%) group. Additionally, METH+CORT significantly increased neurodegeneration above the other three METH treatment groups (≈ 2.5-fold in the parietal cortex). Thus, maintaining elevated levels of glucose during METH exposure increases lethality and may exacerbate neurodegeneration. Neuroinflammation, specifically microglial activation, was associated with degenerating neurons in the parietal cortex and thalamus after METH exposure. The activated microglia in the parietal cortex were surrounding vasculature in most cases and the extent of microglial activation was exacerbated by CORT pretreatment. Our findings show that acute CORT exposure and elevated blood glucose levels can exacerbate METH-induced vascular damage, neuroinflammation, neurodegeneration and lethality. Cover Image for this issue: doi. 10.1111/jnc.13819.

Sevoflurane Induces Coherent Slow-Delta Oscillations in Rats.

Although general anesthetics are routinely administered to surgical patients to induce loss of consciousness, the mechanisms underlying anesthetic-induced unconsciousness are not fully understood. In rats, we characterized changes in the extradural EEG and intracranial local field potentials (LFPs) within the prefrontal cortex (PFC), parietal cortex (PC), and central thalamus (CT) in response to progressively higher doses of the inhaled anesthetic sevoflurane. During induction with a low dose of sevoflurane, beta/low gamma (12-40 Hz) power increased in the frontal EEG and PFC, PC and CT LFPs, and PFC-CT and PFC-PFC LFP beta/low gamma coherence increased. Loss of movement (LOM) coincided with an abrupt decrease in beta/low gamma PFC-CT LFP coherence. Following LOM, cortically coherent slow-delta (0.1-4 Hz) oscillations were observed in the frontal EEG and PFC, PC and CT LFPs. At higher doses of sevoflurane sufficient to induce loss of the righting reflex, coherent slow-delta oscillations were dominant in the frontal EEG and PFC, PC and CT LFPs. Dynamics similar to those observed during induction were observed as animals emerged from sevoflurane anesthesia. We conclude that the rat is a useful animal model for sevoflurane-induced EEG oscillations in humans, and that coherent slow-delta oscillations are a correlate of sevoflurane-induced behavioral arrest and loss of righting in rats.

Differential modulation of thalamo-parietal interactions by varying depths of isoflurane anesthesia.

The thalamus is thought to relay peripheral sensory information to the somatosensory cortex in the parietal lobe. Long-range thalamo-parietal interactions play an important role in inducing the effect of anesthetic. However, whether these interaction changes vary with different levels of anesthesia is not known. In the present study, we investigated the influence of different levels of isoflurane-induced anesthesia on the functional connectivity between the thalamus and the parietal region. Microelectrodes were implanted in rats to record local field potentials (LFPs). The rats underwent different levels of isoflurane anesthesia [deep anesthesia: isoflurane (ISO) 2.5 vol%, light anesthesia (ISO 1 vol%), awake, and recovery state] and LFPs were recorded from four different brain areas (left parietal, right parietal, left thalamus, and right thalamus). Partial directed coherence (PDC) was calculated for these areas. With increasing depth of anesthesia, the PDC in the thalamus-to-parietal direction was significantly increased mainly in the high frequency ranges; however, in the parietal-to-thalamus direction, the increase was mainly in the low frequency band. For both directions, the PDC changes were prominent in the alpha frequency band. Functional interactions between the thalamus and parietal area are augmented proportionally to the anesthesia level. This relationship may pave the way for better understanding of the neural processing of sensory inputs from the periphery under different levels of anesthesia.

Pharmacological blockade of the calcium plateau provides neuroprotection following organophosphate paraoxon induced status epilepticus in rats.

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10mg/kg, i.m.) and carisbamate (90mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury as characterized by Fluoro Jade C labeling was observed in critical brain areas including the dentate gyrus, parietal cortex, amygdala, and thalamus. Dantrolene and carisbamate treatment provided significant neuroprotection against delayed neuronal damage in these brain regions when administered one-hour after POX-SE. These results indicate that dantrolene or carisbamate could be effective adjuvant therapies to the existing countermeasures to reduce neuronal injury and behavioral morbidities post OP SE survival.

Serotonergic modulation of resting state default mode network connectivity in healthy women.

The default mode network (DMN) plays a central role in intrinsic thought processes. Altered DMN connectivity has been linked to diminished cerebral serotonin synthesis. Diminished brain serotonin synthesis is further associated with a lack of impulse control and various psychiatric disorders. Here, we investigated the serotonergic modulation of intrinsic functional connectivity (FC) within the DMN in healthy adult females, controlling for the menstrual cycle phase. Eighteen healthy women in the follicular phase (aged 20-31 years) participated in a double-blind controlled cross-over study of serotonin depletion. Acute tryptophan depletion (ATD) and a balanced amino acid load (BAL), used as the control condition, were applied on two separate days of assessment. Neural resting state data using functional magnetic resonance imaging (fMRI) and individual trait impulsivity scores were obtained. ATD compared with BAL significantly reduced FC with the DMN in the precuneus (associated with self-referential thinking) and enhanced FC with the DMN in the frontal cortex (associated with cognitive reasoning). Connectivity differences with the DMN between BAL and ATD in the precentral gyrus were significantly correlated with the magnitude of serotonin depletion. Right medial frontal gyrus and left superior frontal gyrus connectivity differences with the DMN were inversely correlated with trait impulsivity. These findings partially deviate from previous findings obtained in males and underline the importance of gender-specific studies and controlling for menstrual cycle to further elucidate the mechanism of ATD-induced changes within intrinsic thought processes.

Effect of acupuncture-like stimulation on cortical cerebral blood flow in aged rats.

This study aimed to examine the effect of acupuncture-like stimulation on cortical cerebral blood flow (CBF) in aged rats and the contribution of the intracranial cholinergic vasodilatory system on its response. In urethane-anesthetized rats of 30-37 months of age, manual acupuncture-like stimulation of a forepaw produced an increase in the CBF, independent of systemic arterial pressure. The increase in the CBF induced by forepaw stimulation was abolished by intravenous administration of cholinergic receptor antagonists. Manual acupuncture-like stimulation of a forepaw increased extracellular acetylcholine release in the cerebral cortex. These results suggest that natural somatic afferent stimulation, such as acupuncture-like stimulation, activates the intracranial - most likely, basal forebrain - cholinergic vasodilatory system in the cerebral cortex, even in extremely aged rats.

Green tea extract enhances parieto-frontal connectivity during working memory processing.

RATIONALE: It has been proposed that green tea extract may have a beneficial impact on cognitive functioning, suggesting promising clinical implications. However, the neural mechanisms underlying this putative cognitive enhancing effect of green tea extract still remain unknown. OBJECTIVES: This study investigates whether the intake of green tea extract modulates effective brain connectivity during working memory processing and whether connectivity parameters are related to task performance. MATERIAL AND METHODS: Using a double-blind, counterbalanced, within-subject design, 12 healthy volunteers received a milk whey-based soft drink containing 27.5 g of green tea extract or a milk whey-based soft drink without green tea as control substance while undergoing functional magnetic resonance imaging. Working memory effect on effective connectivity between frontal and parietal brain regions was evaluated using dynamic causal modeling. RESULTS: Green tea extract increased the working memory induced modulation of connectivity from the right superior parietal lobule to the middle frontal gyrus. Notably, the magnitude of green tea induced increase in parieto-frontal connectivity positively correlated with improvement in task performance. CONCLUSIONS: Our findings provide first evidence for the putative beneficial effect of green tea on cognitive functioning, in particular, on working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto-frontal brain connections. Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in psychiatric disorders such as dementia.

Nitric oxide synthase inhibition reverts muscarinic receptor down-regulation induced by pilocarpine- and kainic acid-evoked seizures in rat fronto-parietal cortex.

We investigated how nitric oxide (NO) synthase inhibitor modulates muscarinic receptor expression in epileptic rats. We found that subchronic treatment (4 days) with Nω-nitro-l-arginine reduced the down-regulation of muscarinic receptors induced by pilocarpine and kainic acid in rat fronto-parietal cortex, notwithstanding the dramatic potentiation of seizures induced by both convulsants. Furthermore, functional experiments in fronto-parietal cortex slices, showed that Nω-nitro-l-arginine reduces the down-regulating effect of pilocarpine on carbachol-induced phosphoinositol hydrolysis. Finally, Nω-nitro-l-arginine greatly potentiated the induction of basic fibroblast growth factor (FGF2) by pilocarpine. These data suggest a potential role of NO in a regulatory feedback loop to control muscarinic receptor signal during seizures. The dramatic potentiation of convulsions by NO synthase inhibitors in some animal models of seizures could derive from preventing this feedback loop.

Antioxidant and Nrf2 inducing activities of luteolin, a flavonoid constituent in Ixeris sonchifolia Hance, provide neuroprotective effects against ischemia-induced cellular injury.

Ixeris sonchifolia Hance is an herb distributed in northeastern part of China and has been used by natives to invigorate circulation. In the present study, bioactivity-guided fractionation of I. sonchifolia Hance extract was performed with the aim to isolate and identify the compounds underlying the potential protective effects against ischemia brain injury. Among the four fractions isolated from the herb extract, the ethyl acetate fraction was found to scavenge DPPH radicals, induce ARE-dependent transcriptional activity and upregulate Nrf2 protein levels. The isolation work focused on this fraction revealed the presence of two categories of compounds: flavonoids and sesquiterpene lactones. Among the five isolated flavonoids, luteolin was evaluated to possess direct and indirect antioxidant activities by scavenging free radicals and inducing the upregulation of ARE-dependent phase II enzymes. Concomitant with the findings from the cell-based assays, in the middle cerebral artery occlusion-induced ischemia rat model, administration of luteolin at 4 mg/kg displayed neuroprotective effects by reducing infarct area and inhibiting neuronal cell death. In summary, the obtained results suggest that flavonoids in I. sonchifolia Hance, in particular luteolin, contribute at least partly to the neuroprotective effects against ischemia-induced cellular injury and can be potentially developed for treatment of ischemia-reperfusion induced diseases.

Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3ß/tau signaling pathway and the Aß formation prevention in rats.

Ginsenoside Rg1, one of the major active ingredients isolated from Panax Ginseng, has been shown notable neuroprotective effects in memory impairment animals. However, the role of ginsenoside Rg1 on cognition capacity damaged by neurofibrillary tangles (NFTs) is still poorly understood, and the underlying mechanism remain to be fully elucidated. Okadaic acid (OKA), a potent phosphatase inhibitor, often apply to imitate Alzheimer's disease-like symptom damaged by neurofibrillary tangles, was used to investigate the effects of ginsenoside Rg1 on memory impairment and the related mechanisms in Sprague Dawley (SD) rats. The anti-dementic drug donepezil was used as a positive contrast. The results showed that OKA intracerebroventricular (i.c.v.) injection induced memory impairment, including changes in the ability of orientation navigate, spatial probe and relearning memory in behavioral test of Morris water maze (MWM). However, treatment with Rg1 and donepezil remarkably alleviated these changes. Also OKA treated rats showed memory impairment including increasing of phospho-tau, decreasing of phospho-GSK3ß and the formation of ß-amyloid in special brain regions, which were reversed by Rg1 (20 mg/kg) and donepezil (1 mg/kg) administration. All these indicating that ginsenoside Rg1 protects rats against OKA-induced neurotoxicity. The possible neuroprotective mechanism may be that Rg1 decreases OKA-induced memory impairment through GSK3ß/tau signaling pathway and/or attenuating Aß formation. Thus, these studies indicate that ginsenoside Rg1 might be a potential preventive drug for Alzheimer's disease.

Polydatin--a new mitochondria protector for acute severe hemorrhagic shock treatment.

OBJECTIVE: The aim of the study was find out whether neuronal mitochondrial injury does take place in severe shock and to explore effective therapy for severe shock. RESEARCH DESIGN AND METHODS: Rats were divided in the following group: sham, shock + normal saline (NS), shock + cyclosporine A (CsA), shock + resveratrol (Res) and shock + polydatin (PD). Rats were subjected to shock for 2 h, followed by administration of NS, CsA, Res and PD, and infusion of shed blood. Morphology, metabolism and function of mitochondria were measured. RESULTS: Increased lipid peroxides (LPO) levels, lysosomal injury and mitochondrial permeability transition pore opening took place in neurons, resulting in swollen mitochondria with poorly defined cristae, decreased mitochondrial membrane potential (ΔΨ) and reduced ATP content in shock + NS group, indicating mitochondrial dysfunction. Mitochondrial protectors, such as CsA, Res and PD, partially inhibited these alterations, especially following PD protection, ATP level increased from 44.14 ± 13.81% in shock + NS group to 89.57 ± 9.21% and the survival time was prolonged from 6.3 ± 5.9 h in the shock + NS group to 31.6 ± 13.7 h in shock + PD group. CONCLUSIONS: The study shows that neuronal mitochondrial injury is involved in the genesis of severe shock and PD may be the best choice for protection of neuron against mitochondrial injury in severe shock.

Protective role of vitamins E and C against oxidative stress caused by intermittent cold exposure in aging rat's frontoparietal cortex.

This study examined the role of vitamins E and C in combating oxidative stress (OS) caused by intermittent cold exposure (ICE) in the frontoparietal cortex (FPC) of adult (3 months), late-adult (12 months), middle-aged (18 months) and old (24 months) male Wistar rats. Each age group was divided into sub-groups, control (CON), cold-exposed at 5°C (C5), control supplementees (CON+S) and cold-exposed supplementees (C5+S). The supplement was a daily dose of 400mg vitamin C and 50I.U.of vitamin E/kg body weight. Cold exposure lasted 2h/day for 4 weeks. All age groups except the old showed an increase in the final body mass in the cold-exposed. The feeding efficiency was higher in the cold-exposed irrespective of age. OS as reflected in age-related increased levels of hydrogen peroxide, protein carbonyl, advanced oxidation protein products and malondialdehyde showed further increase with ICE in the FPC. However, vitamins E and C supplementation attenuated the ICE-induced OS. ICE depleted the levels of tissue vitamins E and C while supplementation resulted in increased levels. Further age emerged as a significant factor in ICE-induced stress and also the response to vitamins E and C supplementation. Behavioral studies are underway to examine the findings on ICE-induced oxidative injury in the FPC, and the prospects for using vitamins E and C in cold exposures in the aged.

Ligustilide alleviates brain damage and improves cognitive function in rats of chronic cerebral hypoperfusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustilide (LIG), a main lipophilic component of Danggui (Chinese Angelica root, Radix Angelica sinensis) which is a popular used herb to treat menstrual disorders in traditional chinese medicine, has been reported to possess some neuroprotective effects on permanent focal ischemia and transient forebrain ischemia. AIM OF THE STUDY: Based on previous work, we intended to investigate the protective effects of LIG on parietal cortex and hippocampus of rats in chronic cerebral hypoperfusion model. MATERIALS AND METHODS: Chronic cerebral hypoperfusion was induced by permanent, bilateral common carotid artery's occlusion (2VO). The rats were treated with LIG (80mg/kg, by oral) from the eighth day after surgery for seven consecutive days. Their spatial learning and memory abilities were assessed using the Morris water maze. After six days for maze test, rats were sacrificed. Coronal sections in cortex and hippocampus were stained with cresyl violet or labeled with NeuN (Neuronal Nuclei), MAP-2 (Microtubule-Associated Protein-2), Caspase-3 and GFAP (Glial Fibrillary Acidic Protein) antibodies. RESULTS: LIG treatment for seven days decreased escape latency and swimming distance of 2VO rats from the third day in maze tests, and increased percent time in the target quadrant. LIG prevented neuronal loss, dendrites damage and neuronal apoptosis in both parietal cortex and hippocampus of 2VO rats; and it also inhibited astrocytic activation and proliferation stimulated by hypoperfusion. CONCLUSIONS: These results demonstrate that LIG show obvious neuroprotective potential for treating chronic cerebral hypoperfusion injury, which may be attributed to its anti-apoptosis of neuron and anti-proliferation of astrocyte both in cortex and in hippocampus of 2VO rats. We suggest that LIG can be developed as an effective drugs for the prevention of vascular dementia (VD).

Grey matter changes associated with medication-overuse headache: correlations with disease related disability and anxiety.

OBJECTIVES: Medication-overuse headache (MOH) is associated with psychiatric comorbidities. Neurobiological similarities to substance dependence have been suggested. This study investigated grey matter changes, focussing on pain and reward systems. METHODS: Using voxel-based morphometry, structural MRIs were compared between 29 patients with both, MOH and migraine, according to International Headache Society criteria, and healthy controls. The Migraine Disability Assessment (MIDAS) score was used. Anxiety and depression were screened for with the Hospital Anxiety and Depression Scale (HADS) and confirmed by a psychiatrist, using the Mini International Neuropsychiatric Interview. RESULTS: Nineteen patients (66%) had a present or past psychiatric disorder, mainly affective (N = 11) and anxiety disorders (N = 8). In all patients a significant increase of grey matter volume (GMV) was found in the periaqueductal grey matter of the midbrain, which correlated positively with the MIDAS and the HADS-anxiety subscale. A GMV increase was found bilaterally in the thalamus, and the ventral striatum. A significant GMV decrease was detected in frontal regions including orbitofrontal cortex, anterior cingulate cortex, the left and right insula, and the precuneus. CONCLUSION: These findings are consistent with dysfunction of antinociceptive systems in MOH, which is influenced by anxiety. Dysfunction of the reward system may be a neurobiological basis for dependence in a subgroup of MOH patients.