Ginsenoside Rbl prevents space navigation disability, cortical infarction and thalamic degeneration in rats with focal cerebral ischemia

It was previously reported that prosaposin possesses neurotrophic activity that is ascribed to an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic neuronal damage, the peptide was infused in the left lateral ventricle immediately after occlusion of the left middle cerebral artery (MCA) in stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the ischemia-induced space navigation disability and cortical infarction and prevented secondary thalamic degeneration in a dose-dependent manner. In culture experiments, treatment with the 18-mer peptide attenuated free radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL), and the peptide at higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult. Furthermore, a saposin C fragment comprising the 18-mer peptide bound to synaptosomal fractions of the cerebral cortex, and this binding decreased at the 1st day after MCA occlusion and recovered to the preischemic level at the 7th day after ischemia. These findings suggest that the 18-mer peptide ameliorates neuronal damage in vivo and in vitro through binding to the functional receptor, although the cDNA encoding prosaposin receptor has not been determined yet.

Download Full-text

Temporary Focal Cerebral Ischemia Results in Swollen Astrocytic End-Feet That Compress Microvessels and Lead to Focal Cortical Infarction

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.144 ◽

2011 ◽

Vol 31 (1) ◽

pp. 390-390 ◽

Cited By ~ 1

Author(s):

Umeo Ito ◽

Yoji Hakamata ◽

Emiko Kawakami ◽

Kiyomitsu Oyanagi

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Article Title ◽

Cortical Infarction

Correction to: Journal of Cerebral Blood Flow & Metabolism (2010) 31, 328–338; doi: 10.1038/jcbfm.2010.97; published online 30 June 2010 1. Following the publication of this article, the authors determined that the article title was inaccurate. The new title is ‘Temporary cerebral ischemia results in swollen astrocytic end-feet that compress microvessels and lead to delayed focal cortical infarction.’ 2. Kiyomitsu Oyanagi's institution (3) is in ‘Nagano, Japan’.

Download Full-text

Ciliary neurotrophic factor attenuates spatial cognition impairment, cortical infarction and thalamic degeneration in spontaneously hypertensive rats with focal cerebral ischemia

Neuroscience Letters ◽

10.1016/s0304-3940(96)12450-2 ◽

1996 ◽

Vol 206 (2-3) ◽

pp. 141-144 ◽

Cited By ~ 46

Author(s):

Yoshiaki Kunion ◽

Saburo Sakaki ◽

Hideaki Watanabe ◽

Kei Nakano ◽

Shinsuke Ohta ◽

...

Keyword(s):

Cerebral Ischemia ◽

Spatial Cognition ◽

Neurotrophic Factor ◽

Spontaneously Hypertensive Rats ◽

Focal Cerebral Ischemia ◽

Ciliary Neurotrophic Factor ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Cortical Infarction ◽

Cognition Impairment

Download Full-text

2323 Ciliary neurotrophic factor (CNTF) attenuates spatial cognition impairment, cortical infarction and thalamic degeneration in spontaneously hypertensive rats with focal cerebral ischemia

Neuroscience Research ◽

10.1016/0168-0102(96)89250-9 ◽

1996 ◽

Vol 25 ◽

pp. S245

Author(s):

Yoshiaki Kumon ◽

Saburo Sakaki ◽

Osamu Kadota ◽

Seiji Matsuda ◽

Masahiro Sakanaka

Keyword(s):

Cerebral Ischemia ◽

Spatial Cognition ◽

Neurotrophic Factor ◽

Spontaneously Hypertensive Rats ◽

Focal Cerebral Ischemia ◽

Ciliary Neurotrophic Factor ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Cortical Infarction ◽

Cognition Impairment

Download Full-text

Very Delayed Infarction after Mild Focal Cerebral Ischemia: A Role for Apoptosis?

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199603000-00003 ◽

1996 ◽

Vol 16 (2) ◽

pp. 195-201 ◽

Cited By ~ 445

Author(s):

Cheng Du ◽

Rong Hu ◽

Cynthia A. Csernansky ◽

Chung Y. Hsu ◽

Dennis W. Choi

Keyword(s):

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Tunel Staining ◽

Cortical Infarction ◽

Transient Focal Cerebral Ischemia ◽

Infarction Volume ◽

Limited Degree ◽

The Right ◽

Common Carotid Arteries ◽

Severe Ischemia

The temporal evolution of cerebral infarction was examined in rats subjected to transient occlusion of both common carotid arteries and the right middle cerebral artery. After severe (90-min) ischemia, substantial right-sided cortical infarction was evident within 6 h and fully developed after 1 day. After mild (30-min) ischemia, no cortical infarction was present after 1 day. However, infarction developed after 3 days; by 2 weeks, infarction volume was as large as that induced by 90-min ischemia. These data suggest that infarction after mild focal ischemia can develop in a surprisingly delayed fashion. Some evidence of neuronal apoptosis was present after severe ischemia, but only to a limited degree. However, 3 days after mild ischemia, neurons bordering the maturing infarction exhibited prominent TUNEL staining, and DNA prepared from the periinfarct area of ischemic cortex showed internucleosomal fragmentation. Furthermore, pretreatment with 1 mg/kg cycloheximide markedly reduced infarction volume 2 weeks after mild ischemia. These data raise the possibility that apoptosis, dependent on active protein synthesis, contributes to the delayed infarction observed in rats subjected to mild transient focal cerebral ischemia.

Download Full-text

Continuous Nimodipine Treatment Attenuates Cortical Infarction in Rats Subjected to 24 Hours of Focal Cerebral Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1990.11 ◽

1990 ◽

Vol 10 (1) ◽

pp. 89-96 ◽

Cited By ~ 85

Author(s):

Michael Jacewicz ◽

Steve Brint ◽

Jody Tanabe ◽

William A. Pulsinelli

Keyword(s):

Cerebral Ischemia ◽

Brain Damage ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Spontaneously Hypertensive ◽

Cortical Infarction ◽

Cortical Edema ◽

Tandem Occlusion

Focal cerebral infarction and edema were measured in rats (Wistar, Fisher 344, and spontaneously hypertensive strains) pretreated with nimodipine (2 μg/kg/min i.v.) or its vehicle and subjected to the tandem occlusion of the middle cerebral and common carotid arteries. Animals awoke from anesthesia 10–15 min after onset of ischemia and continued to receive treatment over a 24-h survival period. Cortical infarction and edema were quantified by image analysis of frozen brain sections processed for histology. Nimodipine-treated rats developed 20–60% smaller cortical infarct volumes than controls (p < 0.002). Cortical edema was reduced proportionately to the decrease in infarct volume and constituted ∼36% of the infarct volume. Nimodipine caused a mild hypotensive response that did not aggravate ischemic brain damage. The results indicate that continuous nimodipine treatment, started before induction of focal cerebral ischemia, can attenuate ischemic brain damage and edema as late as 24 h after the onset of ischemia.

Download Full-text

Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats.

Stroke ◽

10.1161/01.str.23.6.894 ◽

1992 ◽

Vol 23 (6) ◽

pp. 894-899 ◽

Cited By ~ 113

Author(s):

D Xue ◽

A Slivka ◽

A M Buchan

Keyword(s):

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Cortical Infarction

Download Full-text

A comparative study of the effects of two nitric oxide synthase inhibitors and two nitric oxide donors on temporary focal cerebral ischemia in the Wistar rat

Journal of Neurosurgery ◽

10.3171/jns.1999.90.2.0332 ◽

1999 ◽

Vol 90 (2) ◽

pp. 332-338 ◽

Cited By ~ 28

Author(s):

Bert A. Coert ◽

Robert E. Anderson ◽

Fredric B. Meyer

Keyword(s):

Nitric Oxide ◽

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

No Donors ◽

Content Type ◽

Cortical Infarction ◽

Nos Inhibitors ◽

Infarction Volume ◽

Nos Inhibitor ◽

Fine Print

Object. A critical review of the literature indicates that the effects of nitric oxide synthase (NOS) inhibitors on focal cerebral ischemia are contradictory. In this experiment the authors methodically examined the dose-dependent effects of two NOS inhibitors and two NO donors on cortical infarction volume in an animal model of temporary focal cerebral ischemia simulating potential ischemia during neurovascular interventions.Methods. Ninety-two Wistar rats underwent 3 hours of combined left middle cerebral artery and bilateral common carotid artery occlusion after having been anesthetized with 1% halothane. A nonselective NOS inhibitor, NG-nitro-l-arginine-methyl-ester (l-NAME), and two NO donors, 3-morpholinosydnonimine hydrochloride and NOC-18, DETA/NO, (Z)-1-[2(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, were administered intravenously 30 minutes before ischemia was induced. A selective neuronal NOS inhibitor, 7-nitroindazole (7-NI), was administered intraperitoneally in dimethyl sulfoxide (DMSO) 60 minutes before ischemia was induced. Two ischemic control groups, to which either saline or DMSO was administered, were also included in this study. Seventy-two hours after flow restoration, the animals were perfused with tetrazolium chloride for histological evaluation.Cortical infarction volume was significantly reduced by 71% in the group treated with 1 mg/kg l-NAME when compared with the saline-treated ischemic control group (27.1 ± 37 mm3 compared with 92.5 ± 26 mm3, p < 0.05). The NOS inhibitor 7-NI significantly reduced cortical infarction volume by 70% and by 92% at doses of 10 and 100 mg/kg: 35.2 ± 32 mm3 (p < 0.05) and 9 ± 13 mm3 (p < 0.005), respectively, when compared with the DMSO-treated ischemic control group (119 ± 43 mm3). There was no significant difference between the saline-treated and DMSO-treated ischemic control groups. Treatment with NO donors did not significantly alter cortical infarction volume.Conclusions. These results support an important role for NO in ischemic neurotoxicity and indicate that neuronal NOS inhibition may be valuable in reducing cortical injury in patients suffering temporary focal cerebral ischemia during neurovascular procedures.

Download Full-text