Keratan sulfate proteoglycan: putative template for neuroblast migratory and axonal fascicular pathways and fetal expression in globus pallidus, thalamus, and olfactory bulb.

Keratan sulfate (KS) is a proteoglycan secreted in the fetal brain astrocytes and radial glia into extracellular parenchyma as granulofilamentous deposits. KS surrounds neurons except dendritic spines, repelling glutamatergic and facilitating GABAergic axons. The same genes are expressed in both neuroblast migration and axonal growth. This study examines timing of KS during morphogenesis of some normally developing human fetal forebrain structures. Twenty normal human fetal brains from 9-41 weeks gestational age were studied at autopsy. KS was examined by immunoreactivity in formalin-fixed paraffin sections, plus other markers including synaptophysin, S-100ß protein, vimentin and nestin. Radial and tangential neuroblast migratory pathways from subventricular zone to cortical plate were marked by KS deposits as early as 9wk GA, shortly after neuroblast migration initiated. During later gestation this reactivity gradually diminished and disappeared by term. Long axonal fascicles of the internal capsule and short fascicles of intrinsic bundles of globus pallidus and corpus striatum also appeared as early as 9-12wk, as fascicular sleeves before axons even entered. Intense KS occurs in astrocytic cytoplasm and extracellular parenchyma at 9wk in globus pallidus, 15wk thalamus, 18wk corpus striatum, 22wk cortical plate, and hippocampus postnatally. Corpus callosum and anterior commissure do not exhibit KS at any age. Optic chiasm shows reactivity at the periphery but not around intrinsic subfasciculi. We postulate that KS forms a chemical template for many long and short axonal fascicles before axons enter and neuroblast migratory pathways at initiation of migration. Cross-immunoreactivity with aggrecan may render difficult molecular distinction.

Volumetric analysis of age- and sex-related changes in the corpus striatum and thalamus in the 1-18 age group: a retrospective magnetic resonance imaging study.

Studies of the development and asymmetry of the corpus striatum and thalamus in early childhood are rare. Studies investigating these structures across the lifespan have not presented their changes during childhood and adolescence in detail. For these reasons, this study investigated the effect of age and sex factors on the development and asymmetry of the corpus striatum and thalamus in the 1-18 age group. In this retrospective study, we included 652 individuals [362 (56%) males] aged 1-18 years with normal brain MRI between 2012 and 2021. Absolute and relative volumes of the corpus striatum and thalamus were obtained by segmentation of three-dimensional T1-weighted MRIs with volBrain1.0. We created age-specific volume data and month-based development models with the help of SPSS (ver.28). The corpus striatum and thalamus had cubic absolute volumetric developmental models. The relative volume of the caudate and thalamus (only males) is consistent with the decreasing "growth" model, the others with the decreasing cubic model. The absolute volumes of the males' bilateral corpus striatum and thalamus and the relative volumes of the caudate and thalamus of the females were significantly larger (P < 0.05). The caudate showed right > left lateralization; putamen, globus pallidus, and thalamus showed left > right lateralization.

3-acetylpyridine induced behavioral dysfunction and neuronal loss in the striatum and hippocampus of adult male rats.

3-acetylpyridine (3-AP) is a neurotoxin that is known to mainly affect the inferior olivary nucleus (ION) in the brain stem. Although several studies have explored the effect of this neurotoxin, still further investigation is required to understand the impact of this toxin on different parts of the brain. In this research, two groups of rats were studied, the 3-AP-treated and the control groups. Behavioral, stereological, and immunohistochemical analyses were performed. The locomotor activity of the 3-AP-treated rats decreased whereas their anxiety levels were higher than in normal controls. Also, memory performance was impaired in animals in the 3-AP group. Microscopic observations showed a decline in the numerical density of neurons in the hippocampus and striatum along with gliosis. Although this toxin is used to affect the ION, it exerts a neurotoxic effect on different brain regions.

Lambda-cyhalothrin enhances inflammation in nigrostriatal region in rats: Regulatory role of NF-κß and JAK-STAT signaling.

The risk to develop neurobehavioural abnormalities in humans on exposure to lambda-cyhalothrin (LCT) - a type II synthetic pyrethroid has enhanced significantly due to its extensive uses in agriculture, homes, veterinary practices and public health programs. Earlier, we found that the brain dopaminergic system is vulnerable to LCT and affects motor functions in rats. In continuation to this, the present study is focused to unravel the role of neuroinflammation in LCT-induced neurotoxicity in substantia nigra and corpus striatum in rats. Increase in the mRNA expression of proinflammatory cytokines (TNF- α, IL-1ß, IL-6) and iNOS whereas decrease in anti-inflammatory cytokine (IL-10) was distinct both in substantia nigra and corpus striatum of rats treated with LCT (0.5, 1.0, 3.0 mg/kg body weight, p.o, for 45 days) as compared to control rats. Further, LCT-treated rats exhibited increased levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), the glial marker proteins both in substantia nigra and corpus striatum as compared to controls. Exposure of rats to LCT also caused alterations in the levels of heat shock protein 60 (HSP60) and mRNA expression of toll-like receptors (TLR2 and TLR4) in the substantia nigra and corpus striatum. An increase in the phosphorylation of key proteins involved in NF-kß (P65, Iκß, IKKα, IKKß) and JAK/STAT (STAT1, STAT3) signaling and alteration in the protein levels of JAK1 and JAK2 was prominent in LCT-treated rats. Histological studies revealed damage of dopaminergic neurons and reactive gliosis as evidenced by the presence of darkly stained pyknotic neurons and decrease in Nissl substance and an increase in infiltration of immune cells both in substantia nigra and corpus striatum of LCT-treated rats. Presence of reactive microglia and astrocytes in LCT-treated rats was also distinct in ultrastructural studies. The results exhibit that LCT may damage dopaminergic neurons in the substantia nigra and corpus striatum by inducing inflammation as a result of stimulation of neuroglial cells involving activation of NF-κß and JAK/STAT signaling.

Implicit Motor Sequence Learning in People with Mild to Moderate Parkinson's Disease: Behavior and Related Brain Function.

BACKGROUND: Deficits in motor learning could be an important explanation for the balance and gait impairments characteristic of people with Parkinson's disease (PD). Empirical studies often report that so-called implicit motor sequence learning is impaired in people with PD, but the results are inconclusive. Altered brain activity during implicit motor sequence learning has also been reported for people with PD in comparison to healthy individuals. OBJECTIVE: To investigate implicit motor sequence learning and associated neural correlates in individuals with mild to moderate PD. METHODS: Fifty-seven participants with PD and 34 healthy participants, all ≥60 years of age, performed the serial reaction time task (SRTT) during the acquisition of functional magnetic resonance imaging (fMRI) data. We analyzed the SRTT as a measure of implicit motor sequence learning in two complementary ways. We analyzed the task-induced fMRI data within regions of interest (ROIs) as well as functional connectivity between ROIs. RESULTS: We found a significant group difference in SRTT performance indicating that the participants with PD had a somewhat lower level of implicit motor sequence learning than the healthy participants. Exploratory analyses suggested that impairments in implicit motor sequence learning for people with PD might be due to a lower learning rate. We did not find any significant group differences in the fMRI data. CONCLUSION: Our exploratory finding of a lower implicit motor learning rate in PD could have important implications for how people with PD should practice new motor tasks and physical exercise. Future studies need to confirm this finding with hypothesis-driven analyses.

Electroacupuncture stimulation attenuates corpus striatum white matter injury in rats with cerebral ischemia by inhibition of Nogo-A/NgR pathway / 针灸推拿医学（英文版）

Objective:To investigate the effect and the mechanism of electroacupuncture(EA)on corpus striatum white matter injury in rats with focal cerebral ischemia(FCI).Methods:Forty-four specific-pathogen-free Sprague-Dawley rats were divided into a normal group(n=10),a sham-operation group(sham group,n=10),and a modeling group(n=24)using the random number table method.The normal group was a blank control.In the sham group,only the vessels and vagus nerve were isolated without embolization.The FCI rat model in the modeling group was replicated using the middle cerebral artery occlusion embolization method.The 20 successfully modeled rats were randomly divided into a model group and an EA group,with 10 rats in each group.Rats in the model group did not receive further treatment.Rats in the EA group received EA stimulation at Baihui(GV20)and the left Zusanli(ST36)24 h after the successful modeling,30 min each time,once a day for 14 d.On the 14th day of the experiment,rats in each group were scored for neurological deficits and then sacrificed,and brain tissues containing corpus striatum around the ischemic focus were paraffin-embedded from 5 rats in each group.Luxol fast blue(LFB)staining was used to detect damage changes in the white matter.The positive immunoreactive expression of myelin basic protein(MBP),myelin-associated growth inhibitor A(Nogo-A)and its receptor(NgR)in rat corpus striatum tissue was detected by immunohistochemistry staining,and then the protein expression of MBP,Nogo-A,and NgR in the corpus striatum tissue around the ischemic focus was determined by Western blotting.Results:Compared with the normal group and the sham group,the model group had a significantly higher neurological deficit score(P＜0.05)and fiber bundle injuries in the corpus striatum white matter,evidenced by a significantly lower mean optical density value of corpus striatum LFB staining(P＜0.05),a significantly lower MBP expression level(P＜0.05),and significantly higher Nogo-A and NgR protein expression levels(P＜0.05).Compared with the model group,the neurological deficit score was significantly lower(P＜0.05),the mean optical density value of LFB staining was significantly higher(P＜0.05),the MBP expression level was increased(P＜0.05),and the expression levels of Nogo-A and NgR proteins were decreased(P＜0.05)in the EA group.Conclusion:EA reduces the ischemia-induced corpus striatum white matter injury and improves neurological deficits.The mechanism may be related to the inhibition of Nogo-A/NgR activation.

Effect of MDMA exposure during pregnancy on cell apoptosis, astroglia, and microglia activity in rat offspring striatum.

Objectives: Ecstasy is a popular recreational psychostimulant with side effects on the central nervous system. This study examined the corpus striatum tissue of adult rats that received ecstasy during the embryonic period for histological and molecular studies. Materials and Methods: Rats were divided into control and ecstasy groups. The ecstasy group was given MDMA 15 mg/kg intraperitoneally twice daily at 8-hour intervals on days 7-15 of gestation. At the age of 15 weeks, adult offspring of both groups were examined for learning and memory study by the Morris water maze test. Then, ventral striatum tissue was harvested for TUNEL assay, Nissl staining, and real-time PCR for the expression of the GFAP and CD11b. Results: Ecstasy up-regulated the GFAP and CD11b expression in the striatum of offspring (*P˂0.05). Furthermore, the Morris water maze test showed that exposure to ecstasy significantly impaired learning and spatial memory (*P˂0.05). TUNEL assay results did not show any significant change in the number of apoptotic cells in the striatum tissue of ecstasy offspring compared with controls, while Nissl staining showed a significant decrease in the number of neurons in the ecstasy group (*P˂0.05). Conclusion: Exposure to ecstasy during pregnancy causes long-lasting changes in brain regions underlying learning and memory, including the striatum, and impaired working memory in the offspring. In addition, these data provide the first evidence that exposure to ecstasy during the embryonic period causes a persistent change in the activity of microglial cells and the number of astrocyte cells in the striatum.

Evaluation of Antioxidants in Discrete Regions of Brain after the Transplantation of Human Amniotic Epithelial Cells in 2,4,5-Trihydroxyphenylethylamine-lesioned Wistar Albino Rats.

Background and Aim: Parkinson's disease (PD) a neurodegenerative disorder for which no preventive or long term effective treatment strategies are available. Epidemiological studies have failed to identify specific environmental, dietary or lifestyle factors for PD. However oxidative stress in the substantia nigra (SN) and Corpus striatum is the most broadly accepted hypothesis for the etiopathology of PD. Many experiments state the notion that augmentation of neurotrophic factors and glial cell-derived neurotrophic factors, could prevent or halt the progress of neurodegeneration in PD. Material and Methods: The present study was designed to assess the motor behaviour with apomorphine injection and level of enzymatic and non-enzymatic antioxidants after transplantation of Human Amniotic Epithelial (HAE) cells in 2,4,5 trihydroxyphenylethylamine (6-OHDA) lesioned striatum in rats. Results: Human Amniotic Epithelial (HAE) cells ameliorated 6-OHDA induced changes in rotational behaviour and modulated the antioxidants. 6-OHDA induced neurotoxicity by the generation of free radicals was pronounced by indication of increased Lipid peroxidation (LPO) levels and decrease in antioxidants level. The present result suggest that increased free radicals and the decrease in the antioxidant defence system possibly lead to structural and functional alterations in membrane-related events and play significant role of the 6-OHDA induced neurotoxicity. In HAE cells transplanted animals the level of LPO was significantly reduced in striatum (36%) and moderately reduced (20%) in midbrain of the 6-OHDA lesioned animals. Conclusion: These alterations were found to be recovered after the HAE cells graft during long term. The 6-OHDA induced neurotoxicity by the generation of free radicals was pronounced by indication of the increased LPO level, decrease in antioxidants and alteration in the dopamine and its metabolites.

Computational Molecular Characterization of the Interaction of Acetylcholine and the NMDA Receptor to Explain the Direct Glycine-Competitive Potentiation of NMDA-Mediated Neuronal Currents.

The activation of N-methyl-d-aspartate receptor (NMDAR) is triggered by the closure of bilobed (D1 and D2) clamshell-like clefts upon binding glycine (Gly) and glutamate. There is evidence that cholinergic compounds modulate NMDAR-mediated currents via direct receptor-ligand interactions; however, molecular bases are unknown. Here, we first propose a mechanistic structure-based explanation for the observed ACh-induced submaximal potentiation of NMDA-elicited currents in striatal neurons by predicting competitive inhibition with Gly. Then, the model was validated, in principle, by confirming that the coapplication of Gly and ACh significantly reduces these neuronal currents. Finally, we delineate the interplay of ACh with the NMDAR by a combination of computational strategies. Crystallographic ACh-bound complexes were studied, revealing a similar ACh binding environment on the GluN1 subunit of the NMDAR. We illustrate how ACh can occupy X-ray monomeric open, dimeric "semiopen" cleft conformations obtained by molecular dynamics and a full-active cryo-EM NMDAR structure, explaining the suboptimal NMDAR electrophysiological activity under the "Venus Flytrap model". At an evolutionary biology level, the binding mode of ACh coincides with that of the homologous ornithine-bound periplasmic LAO binding protein complex. Our computed results indicate an analogous mechanism of action, inasmuch as ACh may stabilize the GluN1 subunit "semiclosed" conformations by inducing direct and indirect D1-to-D2 interdomain bonds. Additionally, an alternative binding site was detected, shared by the known NMDAR allosteric modulators. Experimental and computed results strongly suggest that ACh acts as a Gly-competitive, submaximal potentiating agent of the NMDAR, possibly constituting a novel chemotype for multitarget-directed drug development, e.g., to treat Alzheimer's, and it may lead to a new understanding of glutamatergic neurotransmission.

Long-segment common carotid occlusion presenting with limb-shaking transient ischemic attack: Case report.

Background: Limb-shaking transient ischemic attack (LS-TIA) is a rare manifestation of carotid artery occlusion. Common carotid artery occlusion (CCAO) is a relatively rare condition, and both its natural history and recommendations for treatment are still unclear. Case description: A 67-year-old female suffered from transient episodes of unilateral limb shaking. Computer tomographic angiography (CTA) showed long-segment occlusion of the right common carotid artery. Computer tomographic perfusion (CTP) demonstrated hypoperfusion of the corpus striatum, which suggests that hemodynamic failure is a potential mechanism underlying the LS-TIA secondary to common carotid artery occlusion. The occlusion was successfully recanalized by retrograde common carotid endarterectomy, and the episodes of left limb shaking disappeared after surgery. Conclusions: The occlusion was successfully recanalized by retrograde common carotid endarterectomy, and the episodes of left limb shaking disappeared after surgery. Hypoperfusion of the corpus striatum might be a potential mechanism underlying the LS-TIA secondary to common carotid occlusion.

Functional magnetic resonance imaging study of drug-resistant medial temporal lobe epilepsy / 中华神经科杂志

Objective:To explore the changes of brain activity in drug-resistant or drug-controlled medial temporal lobe epilepsy patients by the method of functional connectivity density (FCD), and to analyze their correlation with the course of the disease.Methods:According to the definition of drug-resistant epilepsy by the International League Against Epilepsy in 2010, 146 patients with medial temporal lobe epilepsy who were clearly diagnosed as unilateral hippocampal sclerosis in Jinling Hospital, Nanjing University School of Medicine from July 2009 to February 2019 were divided into drug control group ( n=73) and drug-resistant group ( n=73). The 3.0 T resting state functional magnetic resonance scan was performed on all subjects to compare the difference in FCD between the two groups, and calculate the correlation between the FCD value of the brain area and the course of the disease between the two groups of patients. Results:There was significant difference between the two groups in FCD. Compared with the drug control group, the drug-resistant group had significantly lower FCD values in the insula, lenticular nucleus, thalamus, hippocampus and precentral gyrus on the side of the epileptogenic focus. The FCD value of the precuneus on the side of the epileptogenic focus in the drug-resistant group was negatively correlated with the duration ( r=-0.30, P=0.01). Conclusions:The FCD of patients with drug-resistant medial temporal lobe epilepsy was lower than that of the drug control group. In addition, there may be progressive damage to the brain. The difference is helpful for exploring the pathophysiological mechanisms related to drug resistance in patients with medial temporal lobe epilepsy, and finding reliable neuroimaging markers related to drug resistance.

Lipidomics Reveals Dysregulated Glycerophospholipid Metabolism in the Corpus Striatum of Mice Treated with Cefepime.

Cefepime exhibits a broad spectrum of antimicrobial activity and thus is a widely used treatment for severe bacterial infections. Adverse effects on the central nervous system (CNS) have been reported in patients treated with cefepime. Current explanation for the adverse neurobehavioral effect of cefepime is mainly attributed to its ability to cross the blood-brain barrier and competitively bind to the GABAergic receptor; however, the underlying mechanism is largely unknown. In this study, mice were intraperitoneally administered 80 mg/kg cefepime for different periods, followed by neurobehavioral tests and a brain lipidomic analysis. LC/MS-MS-based metabolomics was used to investigate the effect of cefepime on the brain lipidomic profile and metabolic pathways. Repeated cefepime treatment time-dependently caused anxiety-like behaviors, which were accompanied by reduced locomotor activity in the open field test. Cefepime profoundly altered the lipid profile, acyl chain length, and unsaturation of fatty acids in the corpus striatum, and glycerophospholipids accounted for a large proportion of those significantly modified lipids. In addition, cefepime treatment caused obvious alteration in the lipid-enriched membrane structure, neurites, mitochondria, and synaptic vesicles of primary cultured striatal neurons; moreover, the spontaneous electrical activity of striatal neurons was significantly reduced. Collectively, cefepime reprograms glycerophospholipid metabolism in the corpus striatum, which may interfere with neuronal structure and activity, eventually leading to aberrant neurobehaviors in mice.

Iron Deficiency-Induced Changes in the Hippocampus, Corpus Striatum, and Monoamines Levels That Lead to Anxiety, Depression, Sleep Disorders, and Psychotic Disorders.

Iron deficiency anemia caused by severe iron deficiency in infancy is associated with poor health and severe neurological impairment such as mental, motor, social, emotional, neurophysiological, and neurocognitive dysfunction. The behavioral effects of iron deficiency can present themselves in infancy, but they are also found in adulthood. Some behaviors can start in childhood but persist throughout adulthood. The behaviors that are particularly often seen in infants and children include wariness and hesitance, lack of positive affect, and diminished social engagement. The affected behaviors in adults include anxiety, depression, higher complex cogitative tasks, and other psychological disorders. The mechanisms of how iron deficiency affects behavior include affecting the hippocampus, the corpus striatum, and certain neurotransmitters. The hippocampus is a brain region that is essential for memory, learning, and other purposes. The hippocampus is very sensitive to lack of Iron during early development. The corpus striatum dispatches dopamine-rich projects to the prefrontal cortex, and it is involved in controlling executive activities such as planning, inhibitory control, sustained attention, working memory, regulation of emotion, memory storage and retrieval, motivation, and reward. Iron deficiency has been known to cause changes in behavioral and developmental aspects by affecting neurotransmitters such as serotonin, noradrenaline, and dopamine. Iron deficiency causes behavior changes that can present in infancy and, even if corrected postnatally, it can have long-lasting effects well into adulthood.

Cardiac Arrest Induced by Asphyxia Versus Ventricular Fibrillation Elicits Comparable Early Changes in Cytokine Levels in the Rat Brain, Heart, and Serum.

Background Current postresuscitative care after cardiac arrest (CA) does not address the cause of CA. We previously reported that asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) elicit unique injury signatures. We hypothesized that the early cytokine profiles of the serum, heart, and brain differ in response to ACA versus VFCA. Methods and Results Adult male rats were subjected to 10 minutes of either ACA or VFCA. Naives and shams (anesthesia and surgery without CA) served as controls (n=12/group). Asphyxiation produced an ≈4-minute period of progressive hypoxemia followed by a no-flow duration of ≈6±1 minute. Ventricular fibrillation immediately induced no flow. Return of spontaneous circulation was achieved earlier after ACA compared with VFCA (42±18 versus 105±22 seconds; P<0.001). Brain cytokines in naives were, in general, low or undetectable. Shams exhibited a modest effect on select cytokines. Both ACA and VFCA resulted in robust cytokine responses in serum, heart, and brain at 3 hours. Significant regional differences pinpointed the striatum as a key location of neuroinflammation. No significant differences in cytokines, neuron-specific enolase, S100b, and troponin T were observed across CA models. Conclusions Both models of CA resulted in marked systemic, heart, and brain cytokine responses, with similar degrees of change across the 2 CA insults. Changes in cytokine levels after CA were most pronounced in the striatum compared with other brain regions. These collective observations suggest that the amplitude of the changes in cytokine levels after ACA versus VFCA may not mediate the differences in secondary injuries between these 2 CA phenotypes.

The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats.

Introduction: Astrocyte dysfunction is the common pathology failing astrocyte-neuron interaction in neurological diseases, including Parkinson's Disease (PD). The present study aimed to evaluate the impacts of astrocytic dysfunction caused by striatal injections of selective glial toxin L-Aminoadipic Acid (L-AA) on the rats' locomotor activity in normal conditions and under alpha-methyl-p-tyrosine depletion of catecholamines synthesis. Methods: Thirty-three male Wistar rats were used in the experiments. Intrastriatal L-AA injections (100 µg) were performed into the right striatum. Alpha-methyl-p-tyrosine (a-MT, 100 mg/kg, inhibitor of tyrosine hydroxylase) was intraperitoneally injected for catecholamine depletion. The animals were divided into 5 groups, as follows: 1. L-AA treated (n=7), 2. L-AA+a-MT treated (n=5), 3. Sham-operated (n=7), 4. Sham+a-MT treated (n=5), 5. Intact control (n=9). For assessing motor function, open field and beam walking tests were used on the third day after the operation. Neuronal and astrocyte markers (glial fibrillary acidic protein, glutamine synthetase, tyrosine hydroxylase, & neuronal nuclear antigen) were examined in the striatum by immunohistochemistry. Results: Administrating L-AA led to astrocytic degeneration in the striatum. No neuronal death and disruption of dopaminergic terminals were detected. L-AA and a-MT-treated animals' distance traveled was significantly (P=0.047) shorter than the Sham-operated group injected with a-MT. In the walking beam test, the number of unilateral paw slippings was significantly (P<0.01) higher in the L-AA-treated group than Sham-operated animals. Administrating a-MT alone and L-AA did not change rats' performance in walking beam tests. Conclusion: Astrocyte ablation in dopamine depleted striatum resulted in reduced motor activity and asymmetrical gait disturbances. These findings demonstrated the role of astroglia in motor function regulation in the nigrostriatal system and suggest the possible association of glial dysfunction with motor dysfunction in PD. Highlights: The local administration of gliotoxin L-aminoadipate in the striatum of rats causes astrocytic degeneration without affecting the neurons and nigrostriatal fibers.The failure of astrocyte-neuron coupling in the striatum leads to motor dysfunction such as gait disturbances and bradykinesia.The influence of astrocytic degeneration on behavior is preserved and enhanced in dopamine-depleted rats. Plain Language Summary: Astrocytes are the nervous system's cells supporting the function of neurons. The failure of astrocyte-neuron interaction is observed in neurological diseases, including Parkinson's disease. We induced the aminoadipate-induced rat model of astrocytic dysfunction to evaluate the role of these cells in movement regulation. In our study, astrocytic dysfunction led to gait disturbances and impaired motor function. The results suggest a possible role of glial pathology in motor impairment in parkinsonism.

Multi-element Analysis of Brain Regions from South African Cadavers.

Trace elements are vital for a variety of functions in the brain. However, an imbalance can result in oxidative stress. It is important to ascertain the normal levels in different brain regions, as such information is still lacking. Therefore, this study aimed to provide baseline trace element concentrations from a South African population, as well as determine trace element differences between sex and brain regions. Samples from the caudate nucleus, putamen, globus pallidus and hippocampus were analysed using inductively coupled plasma mass spectrometry. Aluminium, antimony, arsenic, barium, boron, cadmium, calcium, chromium, cobalt, copper, iron, lead, magnesium, manganese, mercury, molybdenum, nickel, phosphorus, potassium, selenium, silicon, sodium, strontium, vanadium and zinc were assessed. A multiple median regression model was used to determine differences between sex and regions. Twenty-nine male and 13 female cadavers from a Western Cape, South African population were included (mean age 35 years, range 19 to 45). Trace element levels were comparable to those of other populations, although magnesium was considerably lower. While there were no sex differences, significant anatomical regional differences existed; the caudate nucleus and hippocampus were the most similar, and the globus pallidus and hippocampus the most different. In conclusion, this is the first article to report the trace element concentrations of brain regions from a South African population. Low magnesium levels in the brain may be linked to a dietary deficiency, and migraines, depression and epilepsy have been linked to low magnesium levels. Future research should be directed to increase the dietary intake of magnesium.

Ascorbic acid improves extrapyramidal syndromes and corpus striatal degeneration induced by dopamine-2 receptor inhibition in Wistar rats.

Objectives The prolonged uses of fourth-generation antipsychotics have been implicated in inducing extrapyramidal syndromes characterized by the motor deficit. This was attributed to the loss of dopamine-2 receptor (D2R) signaling. However, ascorbic acid (SVCT2R stimulation) in the brain is proposed to modulate D2R activity. We, therefore, investigated the beneficial roles of ascorbic acid in improving the extrapyramidal symptoms seen in D2R loss. Methods Twenty adult male Wistar rats of average weight 200 g were distributed randomly into four groups. The control (NS) received normal saline for 28 days, Untreated D2R inhibition group (-D2R) received normal saline for seven days and then subsequently received chlorpromazine for 21 days, D2R inhibition group treated with ascorbic acid (-D2R+SVCT2R) received chlorpromazine for 21 days and was subsequently treated with ascorbate for seven days while the withdrawal group (WG) received chlorpromazine for 21 days and subsequently received normal saline for seven days. Motor deficits were assessed using a rotarod and cylinder test. The corpus striatum was harvested, processed, and stained using H&E and Nissl stains. Cellular density was analyzed using Image J software 1.8.0. Results Motor deficit was observed in -D2R animals administered chlorpromazine with less improvement in WG compared to control (p<0.05) in both rotarod and cylinder test. Ascorbic acid (SVCT2R stimulation) significantly (p<0.001) improved the latency of fall and climbing attempts observed in -D2R animals. The density of basophilic trigoid bodies was significantly (p<0.001) restored in -D2R+SVCT2R group, suggesting recovery of neural activity in the corpus striatum. Moreover, the hallmarks of neuronal degeneration were less expressed in the ascorbic acid treatment groups. Conclusions Ascorbic acid putatively ameliorates extrapyramidal symptoms observed in D2R blockage by chlorpromazine in Wistar rats.

The effect of 3-nitropropionic acid on behavioral dysfunction, neuron loss and gliosis in the brain of adult male rats: The case of prefrontal cortex, hippocampus and the cerebellum.

3-nitropropionic acid (3-NP) is a mycotoxin widely used to produce a rat model of Huntington's disease. While there are numerous studies on the effect of this neurotoxin, still further investigation is required to understand the influence of this toxin on different regions of the brain. In the present study, there are two groups of rats of which one is treated with 3-NP. Behavioral, stereological and immunohistochemical analyses were conducted. The results show that locomotor activity is largely affected and anxiety is induced up to a certain level, but there is no gross manifestation of deficit in memory. Microscopic observations illustrate damages in the hippocampus and other parts of the brain. Astrogliosis and glial scars were another finding of this study. In conclusion, although 3-NP can be used as a model of Huntington's disease, it exerts a disseminated effect on different regions of the brain.

Effects of animal handling on striatal DAT availability in rats.

OBJECTIVE: Positron emission tomography (PET) is a non-invasive technique measuring quantification of physiological and biochemical processes in the living organism. However, there are many considerations including anesthesia and fasting to acquire small animal imaging. We aimed to evaluate the effects of anesthesia and fasting of rats in dopamine transporter (DAT) imaging acquisition. METHODS: Male Sprague Dawley (SD) rats aged 7 weeks and weighing 180-260 g were used in this study. Rats were randomly divided by 4 groups. Group A was kept under anesthesia for 40 min and fasted over 12 h. Group B was only fasted over 12 h. Group C was only kept under anesthesia for 40 min. Group D was neither kept under anesthesia nor fasted over 12 h. PET scans were started at 40 min after 18F-FP-CIT injection and obtained for 20 min. Volumes-of-interest for striatum and extrastriatal area were used for 18F-FP-CIT PET analysis. Cerebellum was considered as a reference region. Specific binding ratio (SBR) was calculated as follows: [(uptake of target-uptake of cerebellum)]/(uptake of cerebellum). RESULTS: SBR without fasting and anesthesia (group D) was significantly lower than those of other groups (vs group A, p = 0.0004; vs group B, p = 0.0377; vs group C, p = 0.0134). However, SBRs of extrastriatal area (p = 0.5120) were not affected by fasting and anesthesia. CONCLUSIONS: In conclusion, the SBR of striatum was increased after anesthesia by isoflurane and fasting. When designing an experiment using DAT imaging, the effects of isoflurane and fasting should be considered.