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Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice.
- Source :
-
Scientific reports [Sci Rep] 2016 Oct 12; Vol. 6, pp. 35055. Date of Electronic Publication: 2016 Oct 12. - Publication Year :
- 2016
-
Abstract
- Subarachnoid hemorrhage (SAH) results in significant nerve dysfunction, such as hemiplegia, mood disorders, cognitive and memory impairment. Currently, no clear measures can reduce brain nerve damage. The study of brain nerve protection after SAH is of great significance. We aim to evaluate the protective effects and the possible mechanism of methazolamide in C57BL/6J SAH animal model in vivo and in blood-induced primary cortical neuron (PCNs) cellular model of SAH in vitro. We demonstrate that methazolamide accelerates the recovery of neurological damage, effectively relieves cerebral edema, and improves cognitive function in SAH mice as well as offers neuroprotection in blood- or hemoglobin-treated PCNs and partially restores normal neuronal morphology. In addition, western blot analyses show obviously decreased expression of active caspase-3 in methazolamide-treated SAH mice comparing with vehicle-treated SAH animals. Furthermore, methazolamide effectively inhibits ROS production in PCNs induced by blood exposure or hemoglobin insult. However, methazolamide has no protective effects in morality, fluctuation of cerebral blood flow, SAH grade, and cerebral vasospasm of SAH mice. Given methazolamide, a potent carbonic anhydrase inhibitor, can penetrate the blood-brain barrier and has been used in clinic in the treatment of ocular conditions, it provides potential as a novel therapy for SAH.
- Subjects :
- Animals
Apoptosis drug effects
Blood-Brain Barrier drug effects
Brain Edema etiology
Brain Edema metabolism
Caspase 3 metabolism
Cerebral Cortex drug effects
Cerebral Cortex metabolism
Cognition Disorders etiology
Cognition Disorders metabolism
Disease Models, Animal
Gene Expression Regulation drug effects
Male
Methazolamide pharmacology
Mice
Mice, Inbred C57BL
Neurons drug effects
Reactive Oxygen Species metabolism
Subarachnoid Hemorrhage metabolism
Vasospasm, Intracranial
Brain Edema drug therapy
Cognition Disorders drug therapy
Methazolamide administration & dosage
Neurons cytology
Subarachnoid Hemorrhage complications
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27731352
- Full Text :
- https://doi.org/10.1038/srep35055