Attenuated neuropathology by nilvadipine after middle cerebral artery occlusion in rats.

Kawamura, Shingo; Shirasawa, Mitsuru; Fukasawa, H; Yasui, Nobuyuki

doi:10.1161/01.str.22.1.51

Cited by 33 publications

(14 citation statements)

References 28 publications

(14 reference statements)

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“…These results are consistent with the data we reported previously (36). It was demonstrated that nilvadipine is effective against neuronal dysfunction in focal cerebral ischemia (37). Tanaka et al showed the effect of nilvadipine on the neuronal function of the cat brain after occlusion of the left middle cerebral artery (MCA) for 60 min followed by reperfusion for 90 min (38).…”

Section: Fig 7 Inhibition Of Cell Death By Administration Of Amlodisupporting

confidence: 92%

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Amlodipine and Carvedilol Prevent Cytotoxicity in Cortical Neurons Isolated from Stroke-Prone Spontaneously Hypertensive Rats

2004

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We previously reported that vitamin E prevents apoptosis in neurons during cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats (SHRSP). In this paper, we analyzed the effects of antihypertensives as well as vitamin E, which were added to neuron cultures after reoxygenation (20% O2) following hypoxia (1% O2). When added after hypoxia before reoxygenation, vitamin E conferred significant protection to neuronal cells. It was also shown that vitamin E conferred complete protection from neural cell death when added hypoxia and again before reoxygenation. At higher concentrations of vitamin E, strong neuroprotection was observed. Moreover, we verified that pretreatment with either amlodipine, carvedilol or dipyridamole consistently prevented cell death during hypoxia and reoxygenation (H/R). On the other hand, nilvadipine, a dihydropyridine-type calcium entry blocker, had no apparent effect on neuroprotection during H/R. The order of neuroprotective potency was vitamin E dipyridamole carvedilol amlodipine nilvadipine. In parallel experiments, we examined whether these antihypertensive agents were more effective when combined with vitamin E and dipyridamole. The results suggested that in our in vitro model system, antioxidants were the most important agents for the reduction of oxygen-free radical damage in cortical neurons. though pretreatments using vitamin E reduced this number (3,4). Furthermore, showed that vitamin E conferred similar protection against hypertension and cerebral thrombogenesis in SHRSP (5). SHRSP produce more greater concentrations of hydroxyl radicals than Wistar Kyoto rats (WKY) and thus are highly susceptible to neuronal damage (6). It is therefore possible that antioxidants effectively capture hydroxyl radicals produced during hypoxia and reperfusion, thereby preventing neuronal damage in SHRSP. Horakova et al. (7) substantiated the hypothesis that oxygen-free radical are involved in reoxygenation injury in hippocampal. They confirmed that lipid peroxidation was induced and that antioxi-

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Section: Fig 7 Inhibition Of Cell Death By Administration Of Amlodisupporting

confidence: 92%

“…Dipyridamole is a compound with multiple pharmacological actions, and it has also been reported to have an antioxidative effect (36,37). Our results showed that the effects of co-treatment with vitamin E or dipyridamole were not synergistic (Figs.…”

Section: Fig 7 Inhibition Of Cell Death By Administration Of Amlodimentioning

confidence: 49%

Amlodipine and Carvedilol Prevent Cytotoxicity in Cortical Neurons Isolated from Stroke-Prone Spontaneously Hypertensive Rats

2004

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“…The inhibition of Ca2+ entry into cells may possibly serve as a measure for the treatment of cerebral ischaemia (Meyer et al, 1986;Germano et al, 1987;Kucharczyk et al, 1989;Kawamura et al, 1991 (Alps et al, 1988). On the other hand, nicardipine administered after bilateral carotid artery occlusion did not decrease the neurodegeneration .…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective properties of a protein kinase inhibitor against ischaemia‐induced neuronal damage in rats and gerbils

Satoh

Ikegaki

Suzuki

et al. 1996

British J Pharmacology

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1 The neuroprotective properties of fasudil (HA1077), a novel protein kinase inhibitor, were evaluated in two animal models of cerebral ischaemia: transient bilateral carotid artery occlusion in Mongolian gerbils and cerebral microembolization in rats. 2 The cytoprotective effect of fasudil on delayed neuronal death in gerbils was compared with the effects of nimodipine, a calcium channel antagonist and ozagrel, a thromboxane A2 synthetase inhibitor.The average of the neuronal cell density in the ischaemic control group was 17.8+2.1 cells mm-', whereas fasudil (30 mg kg-') significantly diminished the loss of CAl neurones with the average of the neuronal cell density of 101.0+22.0 cells mm-'; nimodipine (10 mg kg-') and ozagrel (30 mg kg-1) did not significantly protect against the ischaemia-induced neuronal loss. 3 In the rat model, the effects of fasudil on the histological and neurological consequences of cerebral microembolization produced via the injection of microspheres were examined. Twenty-four hours after the injection of microspheres into the internal carotid artery, all animals in the control group showed typical symptoms of stroke. Neurological function was significantly improved in the fasudil-treated animals. In the controls, the infarcted area in a cortical slice selected to include the hippocampal area was 0.25 + 0.01 cm2 (mean+s.e.mean) (43.9+2.4% of cortical section of the half hemisphere); the difference was significant compared to the mean area of 32.7+2.8 and 21.5+4.8% observed in rats treated with fasudil (3, 10 mg kg-'), respectively. Fasudil (10 mg kg-') significantly suppressed the increased water content in ischaemic brain tissues (saline-treated rats, 82.4+0.2% vs fasudil-treated rats, 81.0 + 0.4%). 4 These results suggest that: (i) various protein kinases are involved in the pathogenesis of ischaemic injury; and (ii) the inhibition of protein kinases may be efficacious in preventing neuronal death, thus improving neurological function in the brain damage associated with ischaemic stroke.

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“…44,45) The infarct brain tissue in the left MCA territory was differentiated using 2,3,5-triphenyltetrazolium chloride staining method. 46) Treated rats received 0.25 mg liposomeentrapped fasudil via the cisterna magna 2 h after ischemia insult and control rats received drug-free liposomes.…”

Section: Neuroprotective Effect In a Model Of Is-chemiamentioning

confidence: 99%

Safe and Efficient Drug Delivery System with Liposomes for Intrathecal Application of an Antivasospastic Drug, Fasudil

Ishida

Takanashi

Kojima

2006

Biological & Pharmaceutical Bulletin

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Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents.

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Attenuated neuropathology by nilvadipine after middle cerebral artery occlusion in rats.

Cited by 33 publications

References 28 publications

Amlodipine and Carvedilol Prevent Cytotoxicity in Cortical Neurons Isolated from Stroke-Prone Spontaneously Hypertensive Rats

Amlodipine and Carvedilol Prevent Cytotoxicity in Cortical Neurons Isolated from Stroke-Prone Spontaneously Hypertensive Rats

Neuroprotective properties of a protein kinase inhibitor against ischaemia‐induced neuronal damage in rats and gerbils

Safe and Efficient Drug Delivery System with Liposomes for Intrathecal Application of an Antivasospastic Drug, Fasudil

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