Abstract W MP94: Neuroprotective Effect of Isosteviol Sodium on Focal Cerebral Ischemia in Rats

Background & Objective: Isosteviol is a molecule derived from Steviaside which has been used as sweetener worldwide. In this study, sodium salt of isosteviol (STVNA) was given i.v. in rats hours after the transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to investigate its therapeutic neuroprotective effects. Methods: In male Sprague-Dawley rats 2 hours tMCAO with reperfusion or pMCAO was induced and ischemia were confirmed by a laser doppler flowmetry simultaneously. In dosage study, animals were divided into 6 groups: sham, vehicle, or treatment with STVNA at dosage of 1, 5, 10mg•kg-1 or Edaravone 1 hour before the onset of reperfusion. In therapeutic time window study, animals were divided into 5 groups: sham, vehicle, STVNA (10mg•kg-1) at 0, 2 or 4 hours after reperfusion. In pMCAO study, animals were divided into 5 groups: sham, vehicle or STVNA (10mg•kg-1) at 1, 2 or 4 hours after ischemia. Rats were assessed for neurobehavioral deficits after 24 hours and sacrificed for infarct volume quantitation and histology evaluation. Proteomic analysis of the penumbra area in some rats used a Snaps G2x MS-TOF system. Results: In dosage study, the infarct volume of STVNA 10mg•kg-1 group was significantly less compared either with the vehicle group (22±2% vs 41±5%, p< 0.01) or with the Edaravone group (22±2% vs 30±3%, p< 0.05 ). The therapeutic window study shows that STVNA treated at 4h after reperfusion still has significant effects than vehicle group (32±4% vs 41±5%, p<0.05). In pMCAO study, the infarct volume of STVNA at 4h still decreased comparing the vehicle group(29±5% vs 50±6%, p< 0.05).In all STVNA treated groups the neurobehavioral deficits were significantly improved, and there are more restored NeuN-labeled neurons and alleviated TUNEL positive cells in penumbra in comparing with the vehicle group. Proteomic analysis indicates that proteins involved in various inflammations associated signal pathways were dramatically increased by tMCAO, and then were greatly reduced after treated with STVNA. Conclusions: STVNA exhibited remarkable neuroprotective effects when administered 4 hours after pMCAO or 4 hours after reperfusion of tMCAO. Since STVNA has low systemic toxicity, it may be a better alternative for the treatment of stroke.

Download Full-text

Neuroprotective Effects of Isosteviol Sodium Injection on Acute Focal Cerebral Ischemia in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1379162 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Hui Hu ◽

Xiao ou Sun ◽

Fang Tian ◽

Hao Zhang ◽

Qing Liu ◽

...

Keyword(s):

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Artery Occlusion ◽

Therapeutic Window ◽

Vehicle Group ◽

Neuroprotective Effects ◽

Therapeutic Benefits ◽

Neurobehavioral Deficits ◽

Cerebral Artery Occlusion

Previous report has indicated that isosteviol has neuroprotective effects. However, isosteviol was administered preventively before ischemia and the inclusion criteria were limited. In the present study, a more soluble and injectable form of isosteviol sodium (STVNA) was administered intravenously hours after transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to investigate its neuroprotective effects in rats. The rats were assessed for neurobehavioral deficits 24 hours after ischemia and sacrificed for infarct volume quantification and histology evaluation. STVNA 10 mg·kg−1can significantly reduce the infarct volumes compared with vehicle in animals subjected to tMCAO and is twice as potent as previously reported. Additionally, the therapeutic window study showed that STVNA could reduce the infarct volume compared with the vehicle group when administered 4 hours after reperfusion. A similar effect was also observed in animals treated 4 hours after pMCAO. Assessment of neurobehavioral deficits after 24 hours showed that STVNA treatment significantly reduced neurobehavioral impairments. The number of restored NeuN-labeled neurons was increased and the number of TUNEL positive cells was reduced in animals that received STVNA treatment compared with vehicle group. All of these findings suggest that STVNA might provide therapeutic benefits against cerebral ischemia-induced injury.

Download Full-text

Treatment of embolic stroke in rats with bortezomib and recombinant human tissue plasminogen activator

Thrombosis and Haemostasis ◽

10.1160/th05-07-0477 ◽

2006 ◽

Vol 95 (01) ◽

pp. 166-173 ◽

Cited By ~ 43

Author(s):

Li Zhang ◽

Zheng Zhang ◽

Xianshuang Liu ◽

Ann Hozeska ◽

Nancy Stagliano ◽

...

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Vascular Function ◽

Inflammatory Responses ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Therapeutic Window ◽

Vascular Events ◽

Tissue Plasminogen

SummaryStroke elicits a progressive vascular dysfunction, which contributes to the evolution of brain injury. Thrombolysis with tissue plasminogen activator (tPA) promotes adverse vascular events that limit the therapeutic window of stroke to three hours. Proteasome inhibitors reduce vascular thrombotic and inflammatory events, and consequently protect vascular function. The present study evaluated the neuroprotective effect of bortezomib,a potent and selective inhibitor of the proteasome, alone and in combination with delayed thrombolytic therapy on a rat model of embolic focal cerebral ischemia. Treatment with bortezomib reduces adverse cerebrovascular events including secondary thrombosis,inflammatory responses,and blood brain barrier (BBB) disruption, and hence reduces infarct volume and neurological functional deficit when administrated within 4 h after stroke onset. Combination of bortezomib and tPA extends the thrombolytic window for stroke to6 h, which is associated with the improvement of vascular patency and integrity. Real time RT-PCR of endothelial cells isolated by laser-capture microdissection from brain tissue and Western blot analysis showed that bortezomib upregulates endothelial nitric oxide synthase (eNOS) expression and blocks NF-κB activation. These results demonstrate that bortezomib promotes eNOS dependent vascular protection, and reduces NF-κB dependent vascular disruption, all of which may contribute to neuroprotection after stroke.

Download Full-text

Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects

BMC Neuroscience ◽

10.1186/s12868-021-00659-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sher-Wei Lim ◽

Hui-Chen Su ◽

Tee-Tau Eric Nyam ◽

Chung-Ching Chio ◽

Jinn-Rung Kuo ◽

...

Keyword(s):

Neuronal Apoptosis ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Body Weight Loss ◽

Motor Dysfunction ◽

Vehicle Group ◽

Sprague Dawley ◽

Antibacterial Effects ◽

Neuroprotective Effects ◽

Tnf Α

Abstract Background Ceftriaxone is a β-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. Methods Anesthetized male Sprague–Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn’s Gram staining. These parameters above were measured at 72 h after TBI. Results Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. Conclusions The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Download Full-text

Short Therapeutic Window for MK-801 in Transient Focal Cerebral Ischemia in Normotensive Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199601000-00013 ◽

1996 ◽

Vol 16 (1) ◽

pp. 107-113 ◽

Cited By ~ 64

Author(s):

I. Margaill ◽

S. Parmentier ◽

J. Callebert ◽

M. Allix ◽

R. G. Boulu ◽

...

Keyword(s):

Cerebral Ischemia ◽

Nmda Receptors ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Neuroprotective Activity ◽

Therapeutic Window ◽

Left Middle Cerebral Artery ◽

Mk 801 ◽

Transient Focal Cerebral Ischemia

The present study investigates the role of N-methyl-D-aspartate (NMDA) receptors in a model of transient focal cerebral ischemia in normotensive rats. The left middle cerebral artery and both common carotid arteries were occluded for 60 min. Preliminary studies indicated that this gave reproducible infarctions of the cortex and striatum. These infarctions were the result of severe ischemia followed by complete reperfusion after clamp removal, as showed by striatal tissue Po2 monitoring. Microdialysis indicated that glutamate concentration increased immediately after occlusion and returned to the baseline value 40 min after clamp removal. MK-801 (1 mg kg−1 i.v.), an antagonist of the NMDA glutamatergic receptor, reduced the cortical infarct volume by 29% (p < 0.001) and the striatal infarct volume by 14% (p < 0.05) when given just prior to ischemia, but had no neuroprotective activity when given 30 min after the onset of ischemia. This short therapeutic window for MK-801 suggests that NMDA receptors play only a transient role in reversible focal ischemia in rats.

Download Full-text

Sevoflurane Preconditioning against Focal Cerebral Ischemia

Anesthesiology ◽

10.1097/aln.0b013e3181a1fe68 ◽

2009 ◽

Vol 110 (6) ◽

pp. 1271-1278 ◽

Cited By ~ 59

Author(s):

Jean-Laurent Codaccioni ◽

Lionel J. Velly ◽

Chahrazad Moubarik ◽

Nicolas J. Bruder ◽

Pascale S. Pisano ◽

...

Keyword(s):

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Cerebral Injury ◽

Terminal Deoxynucleotidyl Transferase ◽

Control Group ◽

Sprague Dawley ◽

Nissl Staining ◽

Neuroprotective Effects ◽

Sevoflurane Preconditioning

Background Preconditioning the brain with volatile anesthetics seems to be a viable option for reducing ischemic cerebral injury. However, it is uncertain whether this preconditioning effect extends over a longer period of time. The purpose of this study was to determine if sevoflurane preconditioning offers durable neuroprotection against cerebral ischemia. Methods Rats (Sprague-Dawley) were randomly allocated to two groups: nonpreconditioned control group (n = 44) and preconditioned group (n = 45) exposed to 2.7 vol% sevoflurane (45 min) 60 min before surgery. Animals in both groups were anesthetized with 3.0 vol% sevoflurane and subjected to transient middle cerebral artery occlusion. After 60 min of awake focal ischemia, the filament was removed. Functional neurologic outcome (range 0-18; 0 = no deficit), cerebral infarct size (Nissl staining), and apoptosis (Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling; cleaved caspase-3 staining) were evaluated at 3, 7, and 14 days after ischemia. Results Sevoflurane preconditioning significantly improved functional outcome and reduced infarct volume (109 +/- 43 vs. 148 +/- 56 mm(3)) 3 days after ischemia compared to the control group. However, after 7- and 14-day recovery periods, no significant differences were observed between groups. The number of apoptotic cells was significantly lower in the preconditioned group than in the control group after 3- and 7-day recovery periods. Fourteen days after ischemia, no differences were observed between groups. Conclusion In this model of transient focal cerebral ischemia, sevoflurane preconditioning induced effective but transient neuroprotective effects. Sevoflurane preconditioning also decreased ischemia-induced apoptosis in a more sustained way because it was observed up to 7 days after injury.

Download Full-text

Abstract W P369: Inhibitory Effect of FTY720 on Neuroinflammation in Cerebral Ischemia-reperfusion

Stroke ◽

10.1161/str.45.suppl_1.wp369 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Haoliang Xu ◽

Pratik Shah ◽

Dale Pelligrino ◽

Fernando D Testai

Keyword(s):

Cerebral Ischemia ◽

Water Content ◽

Brain Edema ◽

Leukocyte Adhesion ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Therapeutic Window ◽

Vehicle Group ◽

Leukocyte Trafficking ◽

Cerebral Ischemia Reperfusion

Background: Neuroinflammation is a key contributor to brain injury in cerebral ischemia-reperfusion (CIR). FTY720 has been shown to be neuroprotective in animal stroke models. In most studies, FTY720 treatment was initiated either before or shortly after the cerebral insult. The goal of this study is to investigate the effect of FTY720 on CIR-associated neuroinflammation and outcome using a therapeutic window similar to the one utilized in clinical practice. Methods: We used the rat middle cerebral artery (MCA) occlusion model for CIR. The right MCA was occluded for 1h followed by reperfusion. Animals were treated with vehicle or 0.5 mg/kg FTY720 intraperitoneally at 3h post-reperfusion. Neurobehavioral test battery (scale from 0 to 21 points with lower scores representing increased neurological deficits), grid-walking test, infarct volume, and brain water content were determined 24h post CIR. A cranial window was established at 24h post occlusion and leukocyte trafficking behavior was monitored by direct microscopic observation of surface venules. Pial venular leukocyte adhesion was expressed as the % of vascular area occupied by adherent rhodamine-6G-labeled leukocytes. Statistical analysis was performed by t test. Results: Compared to the vehicle group (n=10), FTY720 animals (n=10) had improved neurological score (8.6±1.9 vs. 13.7±1.9; p<0.001) and better motor performance throughout all subsections of the grid test (p<0.001). FTY720 treatment also decreased infarct volume (vehicle: 342±182; FTY720: 122±138 mm 3 ; p=0.04) and ipsilateral brain edema, measured as water content (vehicle: 84.5±1.05%; FTY720: 79.4±0.87%, p=0.003). Leukocyte trafficking study showed a significant increase in vascular leukocyte adhesion 24 h post reperfusion in the vehicle group which was markedly decreased by FTY720 treatment (sham: 3.0±0.6%; vehicle: 11.4±2.6%; FTY720: 5.2±1.4%; p<0.001). Conclusion: FTY720 given at 3h post reperfusion reduces infarct volume, brain edema, neurological disability, and vascular leukocyte adhesion. These results support the beneficial effect of FTY720 when used in a clinically relevant timeframe and provides direct evidence of the anti-inflammatory effect of FTY720 on CIR.

Download Full-text

Abstract TP84: Comparative Analysis of Genetic and Pharmacological Inhibition of Sirt3 in Post Ischemic Injury

Stroke ◽

10.1161/str.48.suppl_1.tp84 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Rajkumar Verma ◽

Rodney Ritzel ◽

Bruce Liang ◽

Louise McCullough

Keyword(s):

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Ischemia Reperfusion ◽

Pharmacological Study ◽

Ischemic Injury ◽

Target Protein ◽

Cns Injury ◽

Neuroprotective Effects ◽

Pharmacological Inhibition

Background: Sirtuin3 (Sirt3), NAD+-dependent deacetylase, regulates several key proteins in both mitochondria and nucleus. The majority of early studies have shown neuroprotective effects of Sirt3 activation in various models of CNS injury. Recently, it was found that genetic loss of Sirt3 is beneficial in ischemia/reperfusion (I/R) injury. Therefore, this study was designed to explore the effects of both genetic and pharmacological inhibition of Sirt3 in a middle cerebral artery occlusion (MCAo) model of stroke. Methods: Focal cerebral ischemia was induced by transient right MCAo for 60min followed by 0, 6, 24 and 72 hrs of reperfusion. A 72hrs post ischemic injury time point was chosen to measure infarction in various treatment groups. The Sirt3 inhibitor AGK7 (sc- 204281 Santa cruz,) that selectively inhibits Sirt3 over Sirt1 and Sirt2, was given as single intraperitoneal injection (0.15, 0.5 and 1.5mg/kg) 3hrs after stroke onset. Activity or expression of Sirt3, was examined with Sirt3 activity kit or western blot using anti-Sirt3, anti-acetylated lysine antibodies. Results: Sirt3 knockout mice showed a significant reduction in hemispheric infarct volume compared to WT littermate controls (37.72±5.21 vs 52.8±6.76, p<0.05). In the pharmacological study, a dose of 0.5 mg/kg i.p of inhibitor showed significant reduction in Sirt3 activity and but had no neuroprotective effect. Furthermore, a much higher dose (1.5mg/kg i.p) did not show any additional inhibitory effect on sirt3 activity but unexpectedly increased infarct volume (51.8±6.87 vs. 62.56± 7.89, P<0.05) and hemorrhagic transformation. Expression studies showed no overall change in Sirt3 expression in whole cell lysates at 0, 6, 24 or 72 hrs after reperfusion; however the expression pattern and activity varied with time in different subcellular compartments. Summary and Conclusions: Changes in subcellular translocation and activity of Sirt3 after I/R stress suggests it important role in target protein deacetylation in stroke pathophysiology. Surprisingly, genetic deletion but not pharmacological inhibition led to neuroprotection, indicating the need to carefully examine target protein by both genetic and pharmacological approaches.

Download Full-text

Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.1.r286 ◽

1995 ◽

Vol 268 (1) ◽

pp. R286-R292 ◽

Cited By ~ 24

Author(s):

C. Iadecola ◽

F. Zhang ◽

X. Xu

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Artery Occlusion ◽

Doppler Flowmetry ◽

Spontaneously Hypertensive ◽

Oxide Synthase

We sought to determine whether expression of the inducible, calcium-independent isoform of nitric oxide synthase (iNOS) contributes to the tissue damage produced by focal cerebral ischemia. The middle cerebral artery was occluded in halothane-anesthetized spontaneously hypertensive rats. Twenty-four hours later rats received intraperitoneal injections of the iNOS inhibitor aminoguanidine (100 mg/kg twice per day; n = 10) or of aminoguanidine + L-arginine (300 mg/kg four times per day; n = 7), aminoguanidine + D-arginine (n = 7), arginine alone (n = 6), or vehicle (n = 9). Drugs were administered for 3 consecutive days. Infarct volume was determined by image analysis in thionin-stained brain sections 4 days after induction of ischemia. Administration of aminoguanidine reduced infarct volume by 33 +/- 4% (P < 0.05 from vehicle; analysis of variance and Tukey's test), a reduction that was antagonized by coadministration of L- but not D-arginine. Administration of L-arginine alone did not affect infarct size (P > 0.05 vs. vehicle). In separate rats (n = 10), aminoguanidine attenuated calcium-independent NOS activity in the infarct (P < 0.05 vs. vehicle) without affecting calcium-dependent activity (P > 0.05). Aminoguanidine did not affect resting cerebral blood flow or the cerebrovascular vasodilation elicited by hypercapnia, as determined by laser-Doppler flowmetry (n = 4). We conclude that aminoguanidine selectively inhibits iNOS activity in the area of infarction and reduces the volume of the infarct produced by middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Neuroprotective Mechanisms of Calycosin Against Focal Cerebral Ischemia and Reperfusion Injury in Rats

Cellular Physiology and Biochemistry ◽

10.1159/000487031 ◽

2018 ◽

Vol 45 (2) ◽

pp. 537-546 ◽

Cited By ~ 23

Author(s):

Yong Wang ◽

Qianyao Ren ◽

Xing Zhang ◽

Huiling Lu ◽

Jian Chen

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Brca1 Gene ◽

Ischemia And Reperfusion ◽

Ischemia And Reperfusion Injury ◽

Neuroprotective Effects ◽

Cerebral Ischemia And Reperfusion ◽

Tnf Α

Background/Aims: Emerging evidence suggests that autophagy plays important roles in the pathophysiological processes of cerebral ischemia and reperfusion injury. Calycosin, an isoflavone phytoestrogen, possesses neuroprotective effects in cerebral ischemia and reperfusion in rats. Here, we investigated the neuroprotective effects of calycosin against ischemia and reperfusion injury, as well as related probable mechanisms behind autophagy pathways. Methods: A cerebral ischemic and reperfusion injury model was established by middle cerebral artery occlusion in male Sprague-Dawley rats. Neurological scores, infarct volumes, and brain water content were assessed after 24 h reperfusion following 2 h ischemia. Additionally, the expression of the autophagy-related protein p62 and NBR1 (neighbor of BRCA1 gene 1), as well as Bcl-2, and TNF-α in rat brain tissues was measured by RT-PCR, western blotting and immunohistochemical analyses. Results: The results showed that calycosin pretreatment for 14 days markedly decreased infarct volume and brain edema, and ameliorated neurological scores in rats with focal cerebral ischemia and reperfusion. It was observed that levels of p62, NBR1 and Bcl-2 were greatly decreased, and levels of TNF-α significantly increased after ischemia and reperfusion injury. However, calycosin administration dramatically upregulated the expression of p62, NBR1 and Bcl-2, and downregulated the level of TNF-α. Conclusions: All data reveal that calycosin exerts a neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms maybe associated with its anti-autophagic, anti-apoptotic and anti-inflammatory action.

Download Full-text

Abstract 154: Protection from Transient Focal Cerebral Ischemia by Transfusion of Polynitroxylated Pegylated Hemoglobin

Stroke ◽

10.1161/str.44.suppl_1.a154 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Jian Zhang ◽

Suyi Cao ◽

Li Ma ◽

Carleton J Hsia ◽

Raymond C Koehler

Keyword(s):

Vascular Function ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Artery Occlusion ◽

Border Region ◽

Therapeutic Window ◽

Laser Doppler Flow ◽

Transient Focal Cerebral Ischemia ◽

Cerebral Artery Occlusion ◽

Hemispheric Infarct

Polynitroxylation of hemoglobin (Hb) confers superoxide dismutase and catalase mimetic activity and can protect neurons from native Hb and glutamate. Here, we determined if transfusion of polynitroxylated pegylated Hb (PNPH) is protective in the rat filament model of 2 h of middle cerebral artery occlusion (MCAO). Transfusion of 10 ml/kg of PNPH at 20 min of MCAO reduced the median infarct volume in cerebral cortex from 40% (37-47% interquartile range; n=10) in controls to 3% (0-7%; n=10; P<0.001) with PNPH and in striatum from 78% (66-88%) to 34% (0-37%; P<0.001). The therapeutic window was evaluated in a second experiment. Compared to the control median hemispheric infarct volume of 22% (13-34%; n=15), infarct volume was reduced to 7% (3-13%; n=14; P<0.05) when PNPH was transfused at 4 h after MCAO (2 h of reperfusion) but not significantly when transfused at 6 h (8%; 3-35%; n=14) or at 8 h (12%; 10-25%; n=14) after MCAO. To determine whether PNPH might act by promoting vasodilation, pial arteriolar diameter in the distal MCA border region was measured in closed cranial windows during MCAO. With no transfusion, MCAO induced an initial dilation (36±5%; ±SD; n=8) that subsided by 2 h (5±11%). With PNPH transfusion at 20 min of MCAO, the initial dilation (31±8%; n=7) was better maintained at 2 h (21±11%; P<0.02). To determine whether delaying PNPH transfusion until 90 min of MCAO would improve penumbral perfusion, laser-Doppler flow (LDF) was measured in the ischemic border region where the reduction in LDF was less severe than in the core. LDF significantly increased from 48±18% of the pre-ischemic baseline to 67±21% (P<0.005). Thus, PNPH transfusion has a significant therapeutic window for protection from transient MCAO and may act, in part, by stabilizing vascular function and improving collateral blood flow.

Download Full-text