Effects of Fasudil Hydrochloride on Cerebral Blood Flow in Patients with Chronic Cerebral Infarction

Nagata, Ken; Kawakami, Yasushi; Satoh, Y; Watahiki, Yasuhito; Yokoyama, Eisei; Yuya, Hiromichi; Hirata, Y.; Shishido, Fumio; Hatazawa, Jun; Kanno, Iwao

doi:10.1097/00002826-199312000-00003

Cited by 20 publications

(18 citation statements)

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“…Fasudil and hydroxyfasudil improve hemodynamic function by increasing regional cerebral blood flow [22,23] as well as preventing hyperviscosity [24], and upregulating eNOS activity in endothelial cells [9]. Rhokinase is thought to play a role in the mechanisms underlying the occurrence of hemodynamic dysfunctions and inflammatory processes [5][6][7][8][9][10][11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%

“…Benefits observed appear to be mediated by various mechanisms; for example, preventing inflammatory response by inhibiting neutrophil and monocyte infiltration [18,19] and inhibiting the production of O 2À in neutrophils and vessels [20,21]; and improving hemodynamic function by increasing regional cerebral blood flow [22,23], preventing hyperviscosity [24], and upregulating eNOS activity in endothelial cells [9].…”

Section: Introductionmentioning

confidence: 99%

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Effects of fasudil in acute ischemic stroke: Results of a prospective placebo-controlled double-blind trial

Shibuya

Hirai

Seto

et al. 2005

Journal of the Neurological Sciences

253

208

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of fasudil in acute ischemic stroke: Results of a prospective placebo-controlled double-blind trial

Shibuya

Hirai

Seto

et al. 2005

Journal of the Neurological Sciences

253

208

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“…It was also recently shown to be effective and well tolerated in phase 2 trials in patients with stable angina [48] and cerebral ischemic stroke [19]. Fasudil has been shown to improve hemodynamic function, tissue oxygenation, and regional cerebral blood flow [49]. This latter property would be beneficial in lowering intracranial hypertension and thereby reducing the poor outcome of CM in African children, as suggested by Newton et al [50].…”

Section: Figurementioning

confidence: 98%

Rho Kinase Inhibition in Severe Malaria: Thwarting Parasite‐Induced Collateral Damage to Endothelia

et al. 2008

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Acute clinical manifestations of falciparum malaria, such as multiorgan failure and cerebral malaria, occur unpredictably and lead to coma and death within hours if left untreated. Despite the emergency administration of effective antimalarial drugs, 15%-20% of patients die. Other therapeutic approaches are therefore urgently needed. There is increasing evidence that endothelial changes play a key role in the pathogenesis of severe malaria. We therefore used coculture models to study interactions between infected erythrocytes and endothelium. We found that adhesion of Plasmodium falciparum to endothelial cells in vitro activated the Rho kinase signaling pathway, which is strongly involved in various vascular diseases. When added concomitantly with parasites, the Rho kinase inhibitor fasudil (HA-1077), a drug already in clinical use, decreased both NF-kappaB activation and endothelial cell apoptosis. Fasudil also helped to restore endothelial barrier integrity after P. falciparum adhesion. Rho kinase inhibition thus appears to be a promising adjunctive therapeutic approach to the management of severe human malaria.

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“…ROCK inhibitors are currently in use or in human trials for a variety of CNS and non-CNS conditions [37,[79][80][81][82][83][84][85][86][87][88]. Application of ROCK inhibitors in vivo may affect NPC cell-cell association and promote aberrant NPC migration, leading to altered NPC signal transduction.…”

Section: Use Of Rock Inhibitors For Treatment Of Neural Damagementioning

confidence: 99%

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

et al. 2011

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Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB). Following neural injury, they also migrate to the site of damage. This study investigated the role of Rho-dependent kinase (ROCK) on the migration of NPCs in vitro and in vivo. In vitro, using neurospheres or SVZ explants, inhibition of ROCK using Y27632 promoted cell body elongation, process protrusion, and migration, while inhibiting NPC chain formation. It had no effect on proliferation, apoptosis, or differentiation. Both isoforms of ROCK were involved. Using siRNA, knockdown of both ROCK1 and ROCK2 was required to promote NPC migration and morphological changes; knockdown of ROCK2 alone was partially effective, with little/no effect of knockdown of ROCK1 alone. In vivo, infusion of Y27632 plus Bromodeoxyuridine (BrdU) into the lateral ventricle for 1 week reduced the number of BrdU-labeled NPCs in the OB compared with BrdU infusion alone. However, ROCK inhibition did not affect the tangential-to-radial switch of NPC migration, as labeled cells were present in all OB layers. The decrease in NPC number at the OB was not attributed to a decrease in NPCs at the SVZ. However, ROCK inhibition decreased the density of BrdU-labeled cells in the RMS and increased the distribution of these cells to ectopic brain regions, such as the accessory olfactory nucleus, where the majority differentiated into neurons. These findings suggest that ROCK signaling regulates NPC migration via regulation of cell-cell contact and chain migration.

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Effects of Fasudil Hydrochloride on Cerebral Blood Flow in Patients with Chronic Cerebral Infarction

Cited by 20 publications

References 0 publications

Effects of fasudil in acute ischemic stroke: Results of a prospective placebo-controlled double-blind trial

Effects of fasudil in acute ischemic stroke: Results of a prospective placebo-controlled double-blind trial

Rho Kinase Inhibition in Severe Malaria: Thwarting Parasite‐Induced Collateral Damage to Endothelia

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

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