Platelet lysates stimulate angiogenesis, neurogenesis and neuroprotection after stroke

2013 ◽  
Vol 110 (08) ◽  
pp. 323-330 ◽  
Author(s):  
Yael Hayon ◽  
Olga Dashevsky ◽  
Ela Shai ◽  
David Varon ◽  
Ronen Leker
Keyword(s):  
Subventricular Zone ◽  
Tissue Repair ◽  
Artery Occlusion ◽  
Therapeutic Effects ◽  
Brain Ischaemia ◽  
Neuroprotective Effects ◽  
Lateral Ventricles ◽  
Neurological Severity Score ◽  
Ischaemic Brain ◽  
Cerebral Artery Occlusion

SummaryPlatelets contain chemo-attractants and mitogens that have a major role in tissue repair. Therefore we hypothesised that tissue regeneration secondary to activation of endogenous neural stem cells (eNSC) can be enhanced by delivering platelets to the ischaemic brain. To examine these potential therapeutic effects we injected platelet-poor plasma (PPP), fibroblast growth factor (FGF2) and platelet lysate (PLT) to the lateral ventricles after permanent middle cerebral artery occlusion (PMCAO) in rats. The animals were tested with the neurological severity score, and infarct volumes were measured at 90 days post–PMCAO. Immunohistochemistry was used to determine the fate of newborn cells and to count blood vessels in the ischaemic brain. Platelets significantly increased eNSC proliferation and angiogenesis in the subventricular zone (SVZ) and in the peri-lesion cortex. Functional outcome was significantly improved and injury size was significantly reduced in rats treated with PLT suggesting additional neuroprotective effects. In conclusion, local delivery of PLT to the lateral ventricles induces angiogenesis, neurogenesis and neuroprotection and reduces behavioural deficits after brain ischaemia.

scholarly journals Long Course Hyperbaric Oxygen Stimulates Neurogenesis and Attenuates Inflammation after Ischemic Stroke

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ying-Sheng Lee ◽  
Chung-Ching Chio ◽  
Ching-Ping Chang ◽  
Liang-Chao Wang ◽  
Po-Min Chiang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hyperbaric Oxygen ◽  
Artery Occlusion ◽  
Trophic Factors ◽  
Therapeutic Effects ◽  
Ischemic Brain ◽  
Neurological Severity Score ◽  
Group Mobilization ◽  
Long Course ◽  
Cerebral Artery Occlusion

Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.

Neuroprotective effects of nicardipine in a rat model of ischemia and reperfusion

1997 ◽  
Vol 2 (6) ◽  
pp. E4 ◽  
Author(s):  
Mamoru Kittaka ◽  
Steven L. Giannotta ◽  
Vladimir Zelman ◽  
Jorge D. Correale ◽  
Christopher M. DeGiorgio ◽  
...  
Keyword(s):  
Brain Temperature ◽  
Neuron Specific Enolase ◽  
Neuronal Injury ◽  
Artery Occlusion ◽  
Specific Marker ◽  
Neuroprotective Effects ◽  
Doppler Flowmetry ◽  
Ischemic Brain ◽  
Edema Volume ◽  
Cerebral Artery Occlusion

A reversible middle cerebral artery occlusion was performed in rats to determine whether nicardipine, a dihydropyridine voltage-sensitive Ca++ channel (VSCC) antagonist, exerts neuroprotective effects when administered 10 minutes following an ischemic insult, and if it does, whether this is due to its vasodilatory action and effect on cerebral blood flow (CBF) or to direct blockade of Ca++ entry into ischemic brain cells. An increase in the intracellular calcium, [Ca++]i, plays a major role in neuronal injury during cerebral ischemia. Although a large amount of Ca++ enters neurons through the VSCC during ischemia, inconsistent neuroprotective effects have been reported with the antagonists of the VSCC. An intraperitoneal injection of nicardipine (1.2 mg/kg) was administered to rats at 10 minutes after the onset of ischemia, and 8, 16, and 24 hours after occlusion. Cortical CBF was determined by laser-Doppler flowmetry. Neurological and neuropathological examinations were performed after 72 hours. Neuron-specific enolase, a specific marker for the incidence of neuronal injury, was measured in plasma. The CBF in the ischemic core and periphery, as well as brain temperature and physiological parameters, were not affected by nicardipine during occlusion or reperfusion. However, nicardipine treatment significantly improved motor neurological outcome by 32%, and the infarction and edema volume in the pallium as well as the edema volume in the striatum were significantly reduced by 28%, 37%, and 53%, respectively. Nicardipine also significantly reduced the neuron-specific enolase plasma levels by 50%, 42%, and 59% at 24, 48, and 72 hours after the occlusion, respectively. It is concluded that nicardipine may attenuate focal ischemic brain injury by exerting direct neuroprotective and antiedematous effects that do not depend on CBF.

scholarly journals Therapeutic Benefits by Human Mesenchymal Stem Cells (hMSCs) and Ang-1 Gene-Modified hMSCs after Cerebral Ischemia

2007 ◽  
Vol 28 (2) ◽  
pp. 329-340 ◽  
Author(s):  
Toshiyuki Onda ◽  
Osamu Honmou ◽  
Kuniaki Harada ◽  
Kiyohiro Houkin ◽  
Hirofumi Hamada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cerebral Artery ◽  
Human Mesenchymal Stem Cells ◽  
Artery Occlusion ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lesion Volume ◽  
Therapeutic Benefits ◽  
Cerebral Artery Occlusion

Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC- and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome.

Neuroprotective Effects of Propofol in Models of Cerebral Ischemia

2006 ◽  
Vol 104 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Chiara Adembri ◽  
Luna Venturi ◽  
Alessia Tani ◽  
Alberto Chiarugi ◽  
Elena Gramigni ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Mitochondrial Swelling ◽  
Oxygen Glucose Deprivation ◽  
Neuroprotective Effects ◽  
Cerebral Artery Occlusion

Background Propofol (2,6-diisopropylphenol) has been shown to attenuate neuronal injury in a number of experimental conditions, but studies in models of cerebral ischemia have yielded conflicting results. Moreover, the mechanisms involved in its neuroprotective effects are yet unclear. Methods The authors evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-glucose deprivation in CA1 pyramidal cells by transmission electron microscopy. Finally, they evaluated whether propofol could attenuate the infarct size and improve the neurobehavioral outcome in rats subjected to permanent middle cerebral artery occlusion in vivo. Results When present in the incubation medium during oxygen-glucose deprivation and the subsequent 24 h recovery period, propofol (10-100 microM) attenuated CA1 injury in hippocampal slices in vitro. Ca2+-induced brain mitochondrial swelling was prevented by 30-100 microM propofol, and so were the ultrastructural mitochondrial changes in CA1 pyramidal cells exposed to oxygen-glucose deprivation. Twenty-four hours after permanent middle cerebral artery occlusion, propofol (100 mg/kg, intraperitoneal) reduced the infarct size by approximately 30% when administered immediately after and up to 30 min after the occlusion. Finally, propofol administered within 30 min after middle cerebral artery occlusion was unable to affect the global neurobehavioral score but significantly preserved spontaneous activity in ischemic rats. Conclusions These results show that propofol, at clinically relevant concentrations, is neuroprotective in models of cerebral ischemia in vitro and in vivo and that it may act by preventing the increase in neuronal mitochondrial swelling.

scholarly journals Focal Cerebral Ischaemia in the Rat: 1. Description of Technique and Early Neuropathological Consequences following Middle Cerebral Artery Occlusion

1981 ◽  
Vol 1 (1) ◽  
pp. 53-60 ◽  
Author(s):  
A. Tamura ◽  
D. I. Graham ◽  
J. McCulloch ◽  
G. M. Teasdale
Keyword(s):  
Carbon Black ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Occipital Cortex ◽  
Artery Occlusion ◽  
Lateral Part ◽  
Ischaemic Brain ◽  
Ischaemic Brain Damage ◽  
Ischaemic Lesion ◽  
Cerebral Artery Occlusion

A procedure for occluding the stem of the proximal middle cerebral artery of the rat is described. The operation is performed under anaesthesia through a small subtemporal craniectomy. After occlusion, 3 animals were perfused with carbon black and 8 with a FAM fixative (40% formaldehyde, glacial acetic acid, and methanol). The findings were compared with sham-operated animals. Carbon black studies demonstrated an area of impaired perfusion corresponding to the territory of the occluded artery in each animal. Neuropathological studies invariably showed that there was ischaemic brain damage in the cortex and basal ganglia. The frontal cortex was involved in every animal, as was the lateral part of the neostriatum; the sensorimotor and auditory cortex were involved in most animals, whereas the occipital cortex and medial striatum were involved only infrequently. The damage produced by ischaemia could be readily distinguished from the small local lesion seen at the surgical site in sham-operated animals. The ability to produce a consistent focal ischaemic lesion in the rodent brain provides a technical approach that is sufficiently reproducible to enable investigation of the pathophysiology of ischaemia using recently developed autoradiographic and neurochemical methods.

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