Endothelial and mural laminin-α5 contributes to neurovascular integrity maintenance.

BACKGROUND: Laminin-α5, a major component of the basal lamina, is predominantly synthesized by endothelial and mural cells (pericytes and vascular smooth muscle cells) in the CNS. Loss of laminin-α5 in either population fails to induce any abnormalities due to functional redundancy. Thus, the functional significance of laminin-α5 in neurovascular integrity remains unknown. Here, we hypothesize that ablation of laminin-α5 in both endothelial and mural cells increases neurovascular permeability. METHODS: The compound knockout mice were generated by crossing laminin-α5 floxed mice with Tie2-Cre and PDGFRß-Cre, which target endothelial cells and mural cells, respectively. Neurovascular permeability in these mutants was determined with both exogenous and endogenous tracers. Endothelial paracellular and transcellular permeability was assessed by examining the expression of tight junction proteins and transcytosis-associated proteins. In addition, transmission electron microscopy (TEM) was used to visualize tight junction ultrastructure and endothelial caveolae vesicles. Defects in pericytes and astrocytes were investigated by examining pericyte coverage/contact and astrocyte polarity. RESULTS: Elevated neurovascular permeability was observed in the mutants. Subsequent studies found increased Caveolin-1 and decreased major facilitator superfamily domain-containing protein 2a (MFSD2A) expression, but unaltered Claudin-5 or zonula occludens-1 (ZO-1) expression. Consistent with these results, mutant mice exhibited increased endothelial caveolae vesicle number with intact tight junction structure under TEM. Additionally, pericyte coverage and contact were also decreased in the mutant mice, while astrocyte polarity was unaffected. CONCLUSIONS: These results strongly indicate that endothelial and mural cell-derived laminin-α5 actively maintains neurovascular integrity via the transcellular rather than paracellular mechanism.

A dispensable role of oligodendrocyte-derived laminin-α5 in brain homeostasis and intracerebral hemorrhage.

Laminin, a major component of the basal lamina in the CNS, is also expressed in oligodendrocytes (OLs). However, the function of OL-derived laminin remains largely unknown. Here, we performed loss-of-function studies using two OL-specific laminin-α5 conditional knockout mouse lines. Both mutants were grossly normal and displayed intact blood-brain barrier (BBB) integrity. In a mouse model of intracerebral hemorrhage (ICH), control mice and both mutants exhibited comparable hematoma size and neurological dysfunction. In addition, similar levels of hemoglobin and IgG leakage were detected in the mutant brains compared to the controls, indicating comparable BBB damage. Consistent with this finding, subsequent studies revealed no differences in tight junction protein (TJP) and caveolin-1 expression among control and knockout mice, suggesting that neither paracellular nor transcellular mechanism was affected in the mutants. Furthermore, compared to the controls, both mutant lines showed comparable oligodendrocyte number, oligodendrocyte proliferation rate, MBP/MAG levels, and SMI-32 expression, highlighting a minimal role of OL-derived laminin-α5 in OL biology. Together, these findings highlight a dispensable role of OL-derived laminin-α5 in both brain homeostasis and ICH pathogenesis.

Fibroblasts repair blood-brain barrier damage and hemorrhagic brain injury via TIMP2.

The function of fibroblasts in intracerebral hemorrhage (ICH) remains elusive. By targeting Col1α1, a fibroblast-specific marker, we generate mice with ablated Col1α1+ fibroblasts. These mutants show exacerbated blood-brain barrier (BBB) damage, enlarged injury volume, and worse neurological function, highlighting a beneficial role of Col1α1+ fibroblasts in ICH. Echoing these findings, fibroblasts significantly decrease endothelial permeability in an in vitro ICH model. Next, we demonstrate that fibroblasts promote BBB integrity in ICH mainly via up-regulating tight junction proteins without affecting transcytosis-associated proteins, indicating a paracellular rather than transcellular mechanism. A subsequent mechanistic study reveals that the BBB-protective effect of fibroblasts is partially mediated by TIMP metallopeptidase inhibitor 2 (TIMP2). Furthermore, we find that exogenous TIMP2 attenuates BBB disruption in these mutants after ICH. These results suggest that Col1α1+ fibroblasts repair BBB damage in ICH via the paracellular pathway in a TIMP2-dependent manner, and that Col1α1+ fibroblasts and TIMP2 may be targeted in ICH treatment.

Cell-specific expression and function of laminin at the neurovascular unit.

Laminin, a major component of the basal lamina (BL), is a heterotrimeric protein with many isoforms. In the CNS, laminin is expressed by almost all cell types, yet different cells synthesize distinct laminin isoforms. By binding to its receptors, laminin exerts a wide variety of important functions. However, due to the reciprocal and cell-specific expression of laminin in different cells at the neurovascular unit, its functions in blood-brain barrier (BBB) maintenance and BBB repair after injury are not fully understood. In this review, we focus on the expression and functions of laminin and its receptors in the neurovascular unit under both physiological and pathological conditions. We first briefly introduce the structures of laminin and its receptors. Next, the expression and functions of laminin and its receptors in the CNS are summarized in a cell-specific manner. Finally, we identify the knowledge gap in the field and discuss key questions that need to be answered in the future. Our goal is to provide a comprehensive overview on cell-specific expression of laminin and its receptors in the CNS and their functions on BBB integrity.

SMAlow/undetectable pericytes differentiate into microglia- and macrophage-like cells in ischemic brain.

Pericytes are multipotent perivascular cells that play important roles in CNS injury. However, controversial findings exist on how pericytes change and whether they differentiated into microglia-like cells after ischemic stroke. This discrepancy is mainly due to the lack of pericyte-specific markers: the "pericyte" population identified in previous studies contained vascular smooth muscle cells (vSMCs) and/or fibroblasts. Therefore, it remains unclear which cell type differentiates into microglia-like cells after stroke. In this study, lineage-tracing technique was used to mark α-smooth muscle actin (SMA)low/undetectable pericytes, vSMCs, and fibroblasts, and their fates were analyzed after ischemic stroke. We found that SMAlow/undetectable pericytes and fibroblasts but not vSMCs substantially proliferated at the subacute phase after injury, and that SMAlow/undetectable pericyte but not vSMCs or fibroblasts differentiated into Iba1+ cells after ischemic stroke. Further imaging flow cytometry analysis revealed that SMAlow/undetectable pericytes differentiated into both microglia and macrophages at day 7 after stroke. These results demonstrate that SMAlow/undetectable pericytes rather than vSMCs or fibroblasts differentiate into both microglia-like and macrophage-like cells after stroke, suggesting that these pericytes may be targeted in the treatment of ischemic stroke.

In vitro models of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe clinical emergency caused by bleeding into brain parenchyma. Currently, there are no effective treatments to improve ICH outcomes. Developing new therapies for ICH relies on a thorough understanding of ICH pathophysiology and good in vitro models that enable mechanistic research. In this review, we summarized widely used in vitro ICH models and compared their advantages and disadvantages. Next, key questions that need to be answered in future research are discussed. We aim to provide a quick reference/summary of widely used in vitro ICH models and stimulate the development of new ICH models.

Loss of mural cell-derived laminin aggravates hemorrhagic brain injury.

BACKGROUND: Mural cells synthesize and deposit laminin to the basement membrane. To investigate the function of mural cell-derived laminin, we generated a mutant mouse line lacking mural cell-derived laminin (termed PKO). In a previous study, we showed that the PKO mice were grossly normal under homeostatic condition, but developed blood-brain barrier (BBB) breakdown with advanced age (> 8 months), suggesting that these mutants are intrinsically weak. Based on these findings, we hypothesized that PKO mice have exacerbated injuries in pathological conditions. METHODS: Using collagenase-induced intracerebral hemorrhage (ICH) as an injury model, we examined various stroke outcomes, including hematoma volume, neurological function, neuronal death, BBB integrity, paracellular/transcellular transport, inflammatory cell infiltration, and brain water content, in PKO mice and their wildtype littermates at young age (6-8 weeks). In addition, transmission electron microscopy (TEM) analysis and an in vitro ICH model were used to investigate the underlying molecular mechanisms. RESULTS: Compared to age-matched wildtype littermates, PKO mice display aggravated stroke outcomes, including larger hematoma size, worse neurological function, increased neuronal cell death, enhanced BBB permeability, increased transcytosis, and elevated inflammatory cell infiltration. These mutants also exhibit high baseline brain water content independent of aquaporin-4 (AQP4). In addition, mural cell-derived laminin significantly reduced caveolin-1 without affecting tight junction proteins in the in vitro ICH model. CONCLUSIONS: These results suggest that mural cell-derived laminin attenuates BBB damage in ICH via decreasing caveolin-1 and thus transcytosis, regulates brain water homeostasis, and plays a beneficial role in ICH.

Basement membrane and blood-brain barrier.

The blood-brain barrier (BBB) is a highly complex and dynamic structure, mainly composed of brain microvascular endothelial cells, pericytes, astrocytes and the basement membrane (BM). The vast majority of BBB research focuses on its cellular constituents. Its non-cellular component, the BM, on the other hand, is largely understudied due to its intrinsic complexity and the lack of research tools. In this review, we focus on the role of the BM in BBB integrity. We first briefly introduce the biochemical composition and structure of the BM. Next, the biological functions of major components of the BM in BBB formation and maintenance are discussed. Our goal is to provide a concise overview on how the BM contributes to BBB integrity.

Mural cell-derived laminin-α5 plays a detrimental role in ischemic stroke.

At the blood-brain barrier (BBB), laminin-α5 is predominantly synthesized by endothelial cells and mural cells. Endothelial laminin-α5 is dispensable for BBB maintenance under homeostatic conditions but inhibits inflammatory cell extravasation in pathological conditions. Whether mural cell-derived laminin-α5 is involved in vascular integrity regulation, however, remains unknown. To answer this question, we generated transgenic mice with laminin-α5 deficiency in mural cells (α5-PKO). Under homeostatic conditions, no defects in BBB integrity and cerebral blood flow (CBF) were observed in α5-PKO mice, suggesting that mural cell-derived laminin-α5 is dispensable for BBB maintenance and CBF regulation under homeostatic conditions. After ischemia-reperfusion (MCAO) injury, however, α5-PKO mice displayed less severe neuronal injury, including reduced infarct volume, decreased neuronal death, and improved neurological function. In addition, α5-PKO mice also showed attenuated vascular damage (milder BBB disruption, reduced inflammatory cell infiltration, decreased brain edema, and diminished hemorrhagic transformation). Mechanistic studies revealed less severe tight junction protein (TJP) loss and pericyte coverage reduction in α5-PKO mice after ischemia-reperfusion injury, indicating that the attenuated ischemic injury in α5-PKO mice is possibly due to less severe vascular damage. These findings suggest that mural cell-derived laminin-α5 plays a detrimental role in ischemic stroke and that inhibiting its signaling may have a neuroprotective effect.

Laminins and their receptors in the CNS.

Laminin, an extracellular matrix protein, is widely expressed in the central nervous system (CNS). By interacting with integrin and non-integrin receptors, laminin exerts a large variety of important functions in the CNS in both physiological and pathological conditions. Due to the existence of many laminin isoforms and their differential expression in various cell types in the CNS, the exact functions of each individual laminin molecule in CNS development and homeostasis remain largely unclear. In this review, we first briefly introduce the structure and biochemistry of laminins and their receptors. Next, the dynamic expression of laminins and their receptors in the CNS during both development and in adulthood is summarized in a cell-type-specific manner, which allows appreciation of their functional redundancy/compensation. Furthermore, we discuss the biological functions of laminins and their receptors in CNS development, blood-brain barrier (BBB) maintenance, neurodegeneration, stroke, and neuroinflammation. Last, key challenges and potential future research directions are summarized and discussed. Our goals are to provide a synthetic review to stimulate future studies and promote the formation of new ideas/hypotheses and new lines of research in this field.

Inhalable Levofloxacin Liposomes Complemented with Lysozyme for Treatment of Pulmonary Infection in Rats: Effective Antimicrobial and Antibiofilm Strategy.

Treatment of bacterial infections becomes increasingly complicated due to increasing bacterial resistance and difficulty in developing new antimicrobial agents. Emphasis should be laid on improvising the existing treatment modalities. We studied the improved antimicrobial and antibiofilm activity of levofloxacin (LFX) and lysozyme (LYS) in microbiological studies. LFX at sub-minimum inhibitory concentration with LYS eradicated > 85% of preformed biofilm. LFX was actively loaded into the liposomes using pH gradient method and was spray-dried with LYS solution. Percent entrapment of LFX in liposome was > 80% and prolonged cumulative release of 85% LFX at the end of 12 h. In vitro lung deposition study and solid-state characterization for spray dried LFX liposome in combination with LYS (LFX liposome-LYS) was performed. Co-spray dried product had mass median aerodynamic diameter ranging < 5 µm. In pharmacodynamic study, Staphylococcus aureus infected rats were treated with LFX liposome-LYS. Lungs, bronchoalveolar lavage fluid (BALF), and nasal fluid were evaluated for microbial burden. Expression of cytokine levels in BALF and serum were also studied by ELISA. In addition, mRNA expression for lung inflammatory mediators and lung myeloperoxidase activity were carried out. Further, lungs and histological changes were observed grossly. Untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels, and microbial load compared to vehicle control. Conversely, LFX liposome-LYS significantly abated these adverse repercussions. Histology findings were also in agreement of above. Acute toxicity study revealed safeness of LFX liposome-LYS. Our findings confirm LFX liposome-LYS exhibited prolonged, improved antibiofilm and antimicrobial efficacy in treating S. aureus infection.

Understanding mitochondrial biogenesis through energy sensing pathways and its translation in cardio-metabolic health.

Mitochondria play a pivotal role in physiological energy governance. Mitochondrial biogenesis comprises growth and division of pre-existing mitochondria, triggered by environmental stressors such as endurance exercise, caloric restriction, cold exposure and oxidative stress. For normal physiology, balance between energy intake, storage and expenditure is of utmost important for the coordinated regulation of energy homeostasis. In contrast, abnormalities in these regulations render the individual susceptible to cardiometabolic disorders. This review provides a comprehensive coverage and understanding on mitochondrial biogenesis achieved through energy-sensing pathways. This includes the complex coordination of nuclear, cytosolic and mitochondrial events involving energy sensors, transcription factors, coactivators and regulators. It focuses on the importance of mitochondrial biogenesis in cardiometabolic health. Lastly, converging on the benefits of caloric restriction and endurance exercise in achieving cardiometabolic health.

Isolation of Type I and Type II Pericytes from Mouse Skeletal Muscles.

Pericytes are perivascular multipotent cells that show heterogeneity in different organs or even within the same tissue. In skeletal muscles, there are at least two pericyte subpopulations (called type I and type II), which express different molecular markers and have distinct differentiation capabilities. Using NG2-DsRed and Nestin-GFP double-transgenic mice, type I (NG2-DsRed+Nestin-GFP-) and type II (NG2-DsRed+Nestin-GFP+) pericytes have been successfully isolated. However, the availability of these double-transgenic mice prevents the widespread use of this purification method. This work describes an alternative protocol that allows for the easy and simultaneous isolation of type I and type II pericytes from skeletal muscles. This protocol utilizes the fluorescence-activated cell sorting (FACS) technique and targets PDGFRß, rather than NG2, together with the Nestin-GFP signal. Following isolation, type I and type II pericytes show distinct morphologies. In addition, type I and type II pericytes isolated with this new method, like those isolated from the double-transgenic mice, are adipogenic and myogenic, respectively. These results suggest that this protocol can be used to isolate pericyte subpopulations from skeletal muscles and possibly from other tissues.

Pulmonary delivery of synergistic combination of fluoroquinolone antibiotic complemented with proteolytic enzyme: A novel antimicrobial and antibiofilm strategy.

Bacterial resistance remains a major hindrance in treatment with antimicrobial agents. Therefore, we assessed the improved antimicrobial and antibiofilm activity of Levofloxacin (LFX) and Serratiopeptidase (SRP) combinations in in vitro microbiological studies. Further, pharmacodynamic and pharmacokinetic studies of liposomal LFX in combination with SRP (LFX liposome-SRP) were performed in S. aureus infected rats. LFX at sub-MIC with SRP eradicated >90% of the preformed biofilm. The entrapment efficiency of LFX in liposome was >80% and the co-spray dried product had MMAD <5 µm. We observed high LFX concentration in the lung (3.39 µg/ml over 3 h) and AUC/MIC ≥100. In a pharmacodynamic study, untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels and microbial load compared to control. Conversely, LFX liposome-SRP significantly abated these adverse repercussions. Histological findings were also in agreement with these observations. Furthermore, our findings corroborate exhibited improved antibiofilm and antimicrobial efficacy of LFX liposome-SRP in treating S. aureus infection.

Pterostilbene ameliorates intracerebroventricular streptozotocin induced memory decline in rats.

There is strong evidence that mitochondrial dysfunction mediated oxidative stress results in aging and energy metabolism deficits thus playing a prime role in pathogenesis of Alzheimer's disease, neuronal death and cognitive dysfunction. Evidences accrued in empirical studies suggest the antioxidant, anticancer and anti-inflammatory activities of the phytochemical pterostilbene (PTS). PTS also exhibits favourable pharmacokinetic attributes compared to other stilbenes. Hence, in the present study, we explored the neuroprotective role of PTS in ameliorating the intracerebroventricular administered streptozotocin (STZ) induced memory decline in rats. PTS at doses of 10, 30 and 50 mg/kg, was administered orally to STZ administered Sprague-Dawley (SD) rats. The learning and memory tests, Morris water maze test and novel object recognition test were performed which revealed improved cognition on PTS treatment. Further, there was an overall improvement in brain antioxidant parameters like elevated catalase and superoxide dismutase activities, GSH levels, lowered levels of nitrites, lipid peroxides and carbonylated proteins. There was improved cholinergic transmission as evident by decreased acetylcholinesterase activities. The action of ATPases (Na+ K+, Ca2+ and Mg2+) indicating the maintenance of cell membrane potential was also augmented. mRNA expression of battery of genes involved in cellular mitochondrial biogenesis and inflammation showed variations which extrapolate to hike in mitochondrial biogenesis and abated inflammation. The histological findings corroborated the effective role of PTS in countering STZ induced structural aberrations in brain.

Laminin differentially regulates the stemness of type I and type II pericytes.

BACKGROUND: Laminin, a major basement membrane component that has direct contact with pericytes under physiological conditions, actively regulates the proliferation and differentiation/fate determination of pericytes. Recently, two types of pericytes (type I and type II) with different molecular markers and functions have been identified in skeletal muscles. Whether laminin differentially regulates the proliferation and differentiation of these two subpopulations remains unclear. METHODS: Wild-type and pericytic laminin-deficient mice under Nestin-GFP background were used to determine if laminin differentially regulates the proliferation and differentiation of type I and type II pericytes. Specifically, type I and type II pericytes were isolated from these mice, and their proliferation and differentiation were examined in vitro. Moreover, in vivo studies were also performed. RESULTS: We demonstrate that, although laminin inhibits the proliferation of both type I and type II pericytes in vitro, loss of laminin predominantly induces proliferation of type II pericytes in vivo. In addition, laminin negatively regulates the adipogenic differentiation of type I pericytes and positively regulates the myogenic differentiation of type II pericytes in vitro. CONCLUSIONS: Laminin differentially regulates the proliferation and differentiation of type I and type II pericytes.

Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio).

The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish.

Anxiolytic and nootropic activity of Vetiveria zizanioides roots in mice.

BACKGROUND: Vetiveria zizanioides (VZ) (family: Poaceae), an aromatic plant commonly known as "Vetiver" has been used for various ailments. Concerning the various ailments being listed as the traditional uses of VZ, no mention about anxiety and memory was found. OBJECTIVE: The present study examined the anxiolytic and memory enhancing activity of ethanolic extract of V. zizanioides (EEVZ) dried roots in mice. MATERIALS AND METHODS: Activity of EEVZ was assessed using models of anxiety (elevated plus-maze [EPM], light/dark test, hole board test, marble-burying test) and learning and memory (EPM, passive shock avoidance paradigm). RESULTS: EEVZ at doses of 100, 200, and 300 mg/kg b.w. illustrated significant anxiolytic activity indicated by increase in time spent and number of entries in open arm, time spent in lightened area, number of head poking and number marble buried when compared to that of diazepam (1 mg/kg b.w.), a reference standard. The same treatment showed a significant decrease in transfer latency to reach open arm, shock-free zone, and number of mistakes when compared to that of scopolamine (0.3 mg/kg b.w.). EEVZ in all the doses (100, 200, and 300 mg/kg b.w.) significantly decreased mortality in sodium nitrite (250 mg/kg b.w.) induced hypoxia and also significantly increases contraction induced by acetylcholine on rat ileum preparation. CONCLUSION: The result emanated in the present investigation revealed EEVZ possesses significant anxiolytic and nootropic activity by possibly interplaying with neurotransmitters implicated in anxiety and learning and memory.

Therapeutic interventions using a combination of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction in rats: modulation through ATP-sensitive K+ channels and eNOS.

BACKGROUND: Effective diet/drug combinations may show additive or synergistic effects in reducing endothelial risk factors vis-à-vis monotherapies. The study evaluated the effect of combined therapy of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. METHODS: Forty-eight male Wistar rats (180-220 g) were randomized into eight groups; control, sodium arsenite (1.5 mg/kg/day) exposed, sodium arsenite exposure followed by treatment with Telmisartan, omega 3-fatty acids, the combination and/or endothelial modulators for 2 weeks depending on the allocated group. VED was assessed by estimating vascular reactivity. Serum thiobarbituric acid-reactive substances (TBARS), nitrite/nitrate levels, reduced glutathione (GSH) levels, superoxide dismutase (SOD) activity, serum cholesterol and triglyceride levels were also determined. RESULTS: Sodium arsenite produced VED by attenuating acetylcholine-induced endothelial relaxation (% Rmax= 45.36), decreasing levels of serum nitrite/nitrate (9.28 µM/mg protein), GSH (16.06 µg/mg of protein), SOD activity (30.69 units/mg protein) and increasing TBARS (0.19 µM/mg protein) compared with control group. The combined therapy with Telmisartan (10 mg/kg/day) and omega 3-fatty acids (180 mg/kg/day) (% Rmax = 80.93, 13.09 µM/mg protein, 25.93 µg/mg of protein, 57.84 units/mg protein and 0.08 µM/mg protein, respectively) significantly abolished the respective derangements induced by sodium arsenite. Further, this combination significantly prevented rise in serum cholesterol and triglyceride levels that was induced by sodium arsenite. However, the ameliorative effects of this combination were abated by N-omega-nitro-L-arginine methyl ester (L-NAME) and glibenclamide. CONCLUSIONS: Combined therapy of Telmisartan and omega 3-fatty acids attenuated VED, by activating enzyme nitric oxide synthase (eNOS) through opening of ATP-sensitive K(+) channels.

Coenzyme q10 abrogated the 28 days aluminium chloride induced oxidative changes in rat cerebral cortex.

OBJECTIVE: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. MATERIALS AND METHODS: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. RESULTS: Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. CONCLUSION: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3.