scholarly journals GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion

2016 ◽  
Vol 38 (5) ◽  
pp. 1952-1962 ◽  
Author(s):  
Baosheng Huang ◽  
Qingsong Xie ◽  
Xiaocheng Lu ◽  
Tengda Qian ◽  
Shuai Li ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Rat Model ◽  
Cerebral Ischaemia ◽  
Artery Occlusion ◽  
High Dose ◽  
Focal Cerebral Ischaemia ◽  
Ischaemia And Reperfusion ◽  
Cerebral Artery Occlusion

Background/Aims: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS), especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl)-3-(4'-phenylphenoxy) propyl] sarcosine (NFPS) in the rat model of experimental stroke. Methods: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO). The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism. Results: The results showed that high dose of NFPS (H-NFPS) significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO) induction in rats, while, low dose of NFPS (L-NFPS) exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal), a specific GlyR ɑ1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes. Conclusions: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits.

scholarly journals Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion

2016 ◽  
Vol 37 (7) ◽  
pp. 2494-2508 ◽  
Author(s):  
Brad A Sutherland ◽  
Jonas C Fordsmann ◽  
Chris Martin ◽  
Ain A Neuhaus ◽  
Brent M Witgen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Cerebral Ischaemia ◽  
Neurovascular Coupling ◽  
Artery Occlusion ◽  
Ischaemia And Reperfusion ◽  
Cerebral Artery Occlusion

Hyperacute changes in cerebral blood flow during cerebral ischaemia and reperfusion are important determinants of injury. Cerebral blood flow is regulated by neurovascular coupling, and disruption of neurovascular coupling contributes to brain plasticity and repair problems. However, it is unknown how neurovascular coupling is affected hyperacutely during cerebral ischaemia and reperfusion. We have developed a remote middle cerebral artery occlusion model in the rat, which enables multi-modal assessment of neurovascular coupling immediately prior to, during and immediately following reperfusion. Male Wistar rats were subjected to remote middle cerebral artery occlusion, where a long filament was advanced intraluminally through a guide cannula in the common carotid artery. Transcallosal stimulation evoked increases in blood flow, tissue oxygenation and neuronal activity, which were diminished by middle cerebral artery occlusion and partially restored during reperfusion. These evoked responses were not affected by administration of the thrombolytic alteplase at clinically used doses. Evoked cerebral blood flow responses were fully restored at 24 h post–middle cerebral artery occlusion indicating that neurovascular dysfunction was not sustained. These data show for the first time that the rat remote middle cerebral artery occlusion model coupled with transcallosal stimulation provides a novel method for continuous assessment of hyperacute neurovascular coupling changes during ischaemia and reperfusion, and offers unique insight into hyperacute ischaemic pathophysiology.

Reliability of behavioral tests in the middle cerebral artery occlusion model of rat

2018 ◽  
Vol 53 (5) ◽  
pp. 478-490 ◽  
Author(s):  
Junghoon Yu ◽  
Jinkyoo Moon ◽  
Joonyoung Jang ◽  
Jee In Choi ◽  
Jooeun Jung ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Rat Model ◽  
Artery Occlusion ◽  
Behavioral Tests ◽  
Walking Test ◽  
Satisfactory Level ◽  
Cylinder Test ◽  
Cerebral Artery Occlusion

Stroke is one of the leading causes of death and disability worldwide, and its incidence is increasing. To overcome impairment from stroke, translational research for developing new therapeutic technologies has been conducted and middle cerebral artery occlusion (MCAo) in rat is the representative model. Since recovery from neurological impairment in contralateral limbs caused by brain damage is the major goal of treatment, behavioral tests that assess the relevant function are used. To determine therapeutic effect, obtaining reliable results of behavioral assessment is a prerequisite. However, studies on the reliability of behavioral tests in the MCAo rat model and necessity of prior training have not yet been reported. In this study, the authors investigate relative and absolute inter-rater reliabilities of modified neurological severity score (mNSS), cylinder test, and grid-walking test before training and repeated training every week until the reliability of results reached a satisfactory level. The training included repeated learning of the scoring system and decreasing disagreements among the raters. For MCAo modeling, adult male Sprague-Dawley rats were subjected to 90 min of transient MCAo. Six raters conducted behavioral tests via observation of video-recording on sham-operated and MCAo model rats at 3 or 7 days after the intervention. An independent experimenter randomly numbered each video clip to blind the experiment. The results of reliabilities were unacceptable before training and improved to a satisfactory level after 6 weeks of training in all of the tests. In conclusion, mNSS, cylinder test, and grid-walking test on the MCAo rat model are reliable evaluation methods after conducting appropriate training.

Panthenol as neuroprotectant: Study in a rat model of middle cerebral artery occlusion

2010 ◽  
Vol 4 (2) ◽  
pp. 148-152 ◽  
Author(s):  
M. V. Onufriev ◽  
M. Yu. Stepanichev ◽  
N. V. Lazareva ◽  
I. N. Katkovskaya ◽  
A. O. Tishkina ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Rat Model ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion
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