benzofurans and Brain-Infarction

Topics: Adult; Aged; Aged, 80 and over; Benzofurans; Brain Infarction; Diffusion Magnetic Resonance Imaging; Female; Humans; Injections; Ischemic Attack, Transient; Male; Middle Aged; Neuroprotective Agents; Outcome Assessment, Health Care; Severity of Illness Index

Increased microglial NADPH oxidase (NOX

Topics: Animals; Apoptosis; Benzofurans; Blood-Brain Barrier; Body Water; Brain Chemistry; Brain Infarction; Coculture Techniques; Cytokines; Diabetes Complications; Diabetes Mellitus, Experimental; Imidazoles; Male; Microglia; NADPH Oxidase 2; Necrosis; Neurons; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease. In this study, we investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia.. Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70mg/kg dl-NBP by oral gavage for two weeks. Biotinylated dextran amine (BDA) was injected into the contralateral sensorimotor cortex on day 14 after ischemia to trace the sprouting of corticospinal tract (CST) fibers into the denervated cervical spinal cord. The expressions of Nogo-A, Nogo-R, Rho-A, and ROCK in the perilesional cortex, the expressions of BDA, PSD-95, and vGlut1 in the denervated spinal cord, 5-bromo-20-deoxyuridine (BrdU)/DCX-positive cells in the subventricular zone (SVZ) of the injured hemisphere were detected by immunofluorescence. The rats' behavioral abilities were measured on postoperative days 30-32 in the beam-walking, cylinder and sticky label tests.. dl-NBP treatment significantly increased the number and length of crossing CST fibers, enhanced significantly the expression levels of synapse-associated proteins including PSD95 and VGlut-1 in the denervated cervical spinal cord, elevated the number of BrdU+/DCX+ cells in SVZ, and reduced markedly those of Rho-A+, ROCK+, Nogo-A+ and Nogo-R+ cells in perilesional cortex. In addition, dl-NBP improved the behavioral performance of the ischemic rats.. dl-NBP enhanced the behavioral recovery after cerebral ischemia in rats, possibly by increasing axonal growth and neurogenesis.

Topics: Animals; Benzofurans; Biotin; Brain Infarction; Dextrans; Disease Models, Animal; Disks Large Homolog 4 Protein; Doublecortin Protein; Endothelin-1; Male; Motor Activity; Neuronal Plasticity; Nogo Proteins; Nogo Receptor 1; Platelet Aggregation Inhibitors; Psychomotor Performance; Rats; Rats, Wistar; Recovery of Function; Signal Transduction; Stroke; Vesicular Glutamate Transport Protein 1

DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.

Topics: Analysis of Variance; Animals; Antioxidants; Benzofurans; Brain Infarction; Brain Injuries; Cerebral Cortex; Disease Models, Animal; Infarction, Middle Cerebral Artery; Magnetic Resonance Imaging; Male; Nervous System Diseases; Neurologic Examination; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tetrazolium Salts

The role of endocannabinoid signaling in the response of the brain to injury is tantalizing but not clear. In this study, transient middle cerebral artery occlusion (MCAo) was used to produce ischemia/reperfusion injury. Brain content of N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol were determined during MCAo. Whole brain AEA content was significantly increased after 30, 60 and 120 min MCAo compared with sham-operated brain. The increase in AEA was localized to the ischemic hemisphere after 30 min MCAo, but at 60 and 120 min, was also increased in the contralateral hemisphere. 2-Arachidonoylglycerol content was unaffected by MCAo. In a second set of studies, injury was assessed 24 h after 2 h MCAo. Rats administered a single dose (3 mg/kg) of the cannabinoid receptor type 1 (CB1) receptor antagonist SR141716 prior to MCAo exhibited a 50% reduction in infarct volume and a 40% improvement in neurological function compared with vehicle control. A second CB1 receptor antagonist, LY320135 (6 mg/kg), also significantly improved neurological function. The CB1 receptor agonist, WIN 55212-2 (0.1-1 mg/kg) did not affect either infarct volume or neurological score.

Topics: Animals; Arachidonic Acids; Benzofurans; Benzoxazines; Blood Pressure; Brain Chemistry; Brain Infarction; Chromatography, Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Endocannabinoids; Hemodynamics; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Male; Mass Spectrometry; Morpholines; Naphthalenes; Neurologic Examination; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Reperfusion Injury; Rimonabant; Tetrazolium Salts; Time Factors