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Myron D Ginsberg

Publications and source records attributed to Myron D Ginsberg.

At least 19 recordsLinked to original sources
PubMed2006

Pixel-based statistical analysis by a 3D clustering approach: application to autoradiographic images.

Statistical analysis of medical images in experimental laboratories plays an important role in confirming scientific findings and in guiding potential clinical applications. In experimental neuroscience studies, autoradiographic images taken under differing physiological or pathological conditions from replicate animals are often compared in order to detect any significant change in glucose utilization or blood flow and to localize these changes. For these comparisons to be valid and informative, proper statistical procedures are in order. Conventional methods include statistic parametric mapping (SPM) analysis, non-parametric analysis and cluster-analysis. Each method of comparison has a specific purpose. This paper describes an approach that combines these conventional methods and presents a non-parametric statistical procedure based on cluster-analysis for localizing significant differences in autoradiographic data sets. By thresholding cluster sizes rather than pixel values to reject false positives, this approach enhances statistical power. By re-shuffling the data sets to produce the null distribution of a cluster size statistic, the test makes few assumptions as to the statistical properties of the SPM, and thus it is valid under a broad range of conditions. The designed method was tested on autoradiographic images of rats subjected to moderate traumatic brain injury (TBI). Different methods were also performed on the same data sets. Comparison among these methods shows that this method is suitable for the statistical analysis of autoradiographic images.

Animals↗
PubMed2006

The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--I: Physiological responses and safety results.

BACKGROUND AND PURPOSE: In preclinical stroke models, high-dose human albumin confers robust neuroprotection. We investigated the safety and tolerability of this therapy in patients with acute ischemic stroke. METHODS: The ALIAS (Albumin in Acute Stroke) Pilot Clinical Trial used a multiple-tier, open-label, dose-escalation design. Subjects with acute ischemic stroke (NIH Stroke Scale [NIHSS] of 6 or above) received a 2-hour infusion of 25% human albumin (ALB) beginning within 16 hours of stroke onset. Six successive ALB dose tiers were assessed ranging from 0.34 to 2.05 g/kg. Neurologic and cardiac function was sequentially monitored. At 3 months, the NIHSS, modified Rankin Scale, and Barthel Index were measured. RESULTS: Eighty-two subjects (mean age, 65 years) received ALB at 7.8+/-3.4 hours after stroke onset (mean+/-standard deviation). Forty-two patients also received standard-of-care intravenous tissue plasminogen activator (tPA). Vital signs were unaltered by ALB treatment. Dose-related increases in plasma albumin and mild hemodilution were maximal at 4 to 12 hours. Age-related plasma brain natriuretic peptide levels increased at 24 hours after ALB but did not predict cardiac adverse events. The sole ALB-related adverse event was mild or moderate pulmonary edema in 13.4% of subjects, which was readily managed with diuretics. In the tPA-treated subgroup, symptomatic intracranial hemorrhage occurred in only one of 42 subjects. CONCLUSIONS: Twenty-five percent human albumin in doses ranging up to 2.05 g/kg was tolerated by patients with acute ischemic stroke without major dose-limiting complications. tPA therapy did not affect the safety profile of ALB. The companion article presents neurologic outcome data and efficacy analysis in these subjects.

Aged↗
PubMed2006

The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--II: neurologic outcome and efficacy analysis.

BACKGROUND AND PURPOSE: High-dose human albumin (ALB) is robustly neuroprotective in rodent stroke models. A phase I dose-escalation study was conducted to assess the safety of ALB therapy in ischemic stroke. We analyzed the data for preliminary evidence of treatment efficacy. METHODS: Eighty-two subjects with acute ischemic stroke (NIH Stroke Scale [NIHSS] of 6 or above) received 25% ALB beginning within 16 hours of stroke onset. Six successive ALB dose tiers were assessed (range, 0.34 to 2.05 g/kg). Forty-two patients also received standard-of-care intravenous tissue plasminogen activator (tPA). Efficacy outcomes were determined at 3 months. We compared the highest three, putatively therapeutic ALB dose tiers (1.37 to 2.05 g/kg) with the lowest three, presumed subtherapeutic doses (0.34 to 1.03 g/kg) and with historical cohort data derived from the NINDS rt-PA Stroke Study. RESULTS: After adjusting for the tPA effect, the probability of good outcome (defined as modified Rankin Scale 0 to 1 or NIH Stroke Scale 0 to 1 at 3 months) at the highest three ALB doses was 81% greater than in the lower dose-tiers (relative risk [RR], 1.81; 95% confidence interval [CI], 1.11 to 2.94) and was 95% greater than in the comparable NINDS rt-PA Stroke Study cohort (RR, 1.95; 95% CI, 1.47 to 2.57). The tPA-treated subjects who received higher-dose ALB were three times more likely to achieve a good outcome than subjects receiving lower-dose ALB, suggesting a positive synergistic effect between ALB and tPA. CONCLUSIONS: Our data suggest that high-dose ALB therapy may be neuroprotective after ischemic stroke. These results have led to a multicenter, randomized, placebo-controlled efficacy trial of ALB in acute ischemic stroke-the ALIAS Phase III Trial.

Aged↗
PubMed2005

Astrocytes react to oligemia in the forebrain induced by chronic bilateral common carotid artery occlusion in rats.

The effects of oligemia (moderate ischemia) on the brain need to be explored because of the potential role of subtle microvascular changes in vascular cognitive impairment and dementia. Chronic bilateral common carotid artery occlusion (BCCAO) in adult rats has been used to study effects of oligemia (hypoperfusion) using neuropathological and neurochemical analysis as well as behavioral tests. In this study, BCCAO was induced for 1 week, or 2, 4, and 6 months. Sensitive immunohistochemistry with marker proteins was used to study reactions of astrocytes (GFAP, nestin), and lectin binding to study microglial cells during BCCAO. Overt neuronal loss was visualized with NeuN antibodies. Astrocytes reacted to changes in the optic tract at all time points, and strong glial reactions also occurred in the target areas of retinal fibers, indicating damage to the retina and optic nerve. Astrocytes indicated a change in the corpus callosum from early to late time points. Diffuse increases in GFAP labeling occurred in parts of the neocortex after 1 week of BCCAO, in the absence of focal changes of neuronal marker proteins. No significant differences emerged in the cortex at longer time points. Nestin labeling was elevated in the optic tract. Reactions of microglia cells were seen in the cortex after 1 week. Measurements of the basilar artery indicated a considerable hypertrophy, indicative of macrovascular compensation in the chronic occlusion model. These results indicate that chronic BCCAO and, by inference, oligemia have a transient effect on the neocortex and a long-lasting effect on white matter structures.

Animals↗
PubMed2005

A selective endothelin ET(A) receptor antagonist, SB 234551, improves cerebral perfusion following permanent focal cerebral ischemia in rats.

In recent experimental studies, a selective antagonist of endothelin ET(A) receptors, SB 234551, improved neurological and histological outcome in both head trauma and transient focal cerebral ischemia. The present study was conducted to ascertain the degree to which hemodynamic alterations are responsible for this therapeutic effect in a model of permanent middle cerebral artery occlusion (MCAo) in rats. Anesthetized Sprague-Dawley rats were subjected to permanent MCAo by insertion of an intraluminal nylon suture coated with poly-L-lysine. The agent (SB 234551, 30 microg/kg/min = 1.8 mg/kg/h) or vehicle (PBS; 0.6 ml/h) was administered by i.v. infusion beginning 15 min after onset of MCAo and lasting for 23.75 h. Autoradiographic measurement of local cerebral blood flow (lCBF) was performed at 24 h. Physiological data were similar among groups. SB 234551 augmented perfusion by 1.7- to 1.8-fold in both the ischemic hemisphere and in the contralateral (non-ischemic) hemisphere when compared to vehicle-treated ischemic animals. In the ischemic hemisphere, the brain regions significantly benefited were those lying outside the zone of most dense ischemia (i.e., paramedian cortex and thalamus), while in the non-ischemic hemisphere all regions measured showed significant lCBF augmentation. This study demonstrates that SB 234551 therapy results in significant improvement of local cerebral perfusion in the ischemic as well as in the non-ischemic hemispheres after permanent MCAo.

Animals↗
PubMed2005

Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoietic protein, in focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for treating anemia. In animal models, exogenous recombinant human erythropoietin has been reported to be beneficial in treating experimental cerebral ischemia. In this study, we determined whether darbepoetin alfa would protect in a rat model of transient focal cerebral ischemia. METHODS: Rats received 2-hour middle cerebral artery suture-occlusion. The drug (darbepoetin alfa, 10 microg/kg) or vehicle was administered intraperitoneally 2 hours after onset of middle cerebral artery occlusion. Animals were allowed to survive for 3 or 14 days. Behavioral tests were performed sequentially. Infarct volumes and brain swelling were determined. RESULTS: Darbepoetin alfa-treated rats showed improved neuroscores relative to vehicle-treated animals beginning within 1 hour of treatment and persisting throughout the 14-day survival period. Darbepoetin alfa significantly reduced corrected total (cortical + subcortical) infarct volume (56.3+/-20.6 and 110.8+/-6.8 mm3, respectively) and total infarct areas at multiple levels compared with vehicle in the 14-day survival group. Brain swelling was not affected by treatment. CONCLUSIONS: Darbepoetin alfa confers behavioral and histological neuroprotection after focal ischemia in rats.

Animals↗
PubMed2005

Stilbazulenyl nitrone, a second-generation azulenyl nitrone antioxidant, confers enduring neuroprotection in experimental focal cerebral ischemia in the rat: neurobehavior, histopathology, and pharmacokinetics.

Stilbazulenyl nitrone (STAZN) is a potent lipophilic second-generation azulenyl nitrone antioxidant, which is highly neuroprotective in rodent models of cerebral ischemia and trauma. This study was conducted to establish whether the neuroprotection induced by STAZN persists with chronic survival and to characterize STAZN's pharmacokinetics. Physiologically regulated rats received a 2-h middle cerebral artery occlusion by intraluminal suture and were treated with either STAZN [four 0.6 mg/kg doses i.p. administered at 2 (i.e., onset of recirculation), 4, 24, and 48 h; n = 16] or dimethyl sulfoxide vehicle (n = 11). They received sequential neurobehavioral examinations followed by quantitative neuropathology at 30 days. STAZN improved neurological deficits compared with vehicle controls, beginning within <2 h of the first dose and persisting throughout a 30-day survival. Large cystic necrotic infarcts were common in vehicle-treated rats but infrequent in STAZN-treated rats, and noninfarcted forebrain tissue was increased on average by 15%. In normal rats administered 5 mg/kg STAZN i.v. in Solutol HS 15/ethanol/saline vehicle, STAZN blood levels exhibited a biexponential decline, with an initial half-life of 28 min and a subsequent slow decay with half-life of approximately 7 h. STAZN tissue levels at 2 to 3 h were, on average, 2.5% of blood levels in forebrain, 56% in myocardium, and 41% in kidney. STAZN was concentrated in liver with initial concentrations averaging 5.2-fold above blood levels and a subsequent linear decline of 40% between 24 and 72 h. These results establish that STAZN confers enduring ischemic neuroprotection, has a long circulating half-life, and penetrates well into brain and other organs-characteristics favoring its potential therapeutic utility.

Animals↗
PubMed2005

Albumin treatment reduces neurological deficit and protects blood-brain barrier integrity after acute intracortical hematoma in the rat.

BACKGROUND AND PURPOSE: Acute intracerebral hemorrhage (ICH) is a common and severe form of stroke. To date, medical management of ICH has had scant impact on morbidity and mortality. Because albumin therapy is markedly neuroprotective in preclinical models of ischemic stroke, and because ischemic and hemorrhagic stroke share several common injury mechanisms, we hypothesized that albumin therapy might also benefit ICH. METHODS: Acute intracortical hematoma was produced in anesthetized, normothermic rats by the single stereotaxic injection of 50 muL of autologous, nonheparinized whole blood over 5 minutes. Separate animal groups were treated either with 25% human albumin, 1.25 g/kg, or with intravenous saline vehicle at 60 minutes after ICH. Neurobehavior was quantified sequentially over the next 2 to 7 days. Damage to the blood-brain barrier was assessed at 2 days after ICH by fluorometric measurement of Evans blue extravasation in dissected brain regions. RESULTS: High-grade neurological deficits were present in all rats at 50 minutes after ICH (score 10.3+/-0.2, mean+/-SEM [maximal score 12]). Albumin-treated rats showed improved neuroscores relative to saline-treated animals beginning within hours of treatment and persisting throughout the 7-day survival period. At 3 and 7 days, mean total neuroscores of the albumin group were 38% to 43% lower than in saline-treated animals. Perihematomal Evans blue discoloration was readily evident in saline-treated ICH rats but was reduced by albumin treatment. Hemispheric Evans blue content ipsilateral to the hematoma was reduced by 49% by albumin treatment (albumin 93.9+/-13.3 versus saline 184.7+/-33.7 mg/g, P<0.05). Hematoma volume and brain swelling were not affected by albumin treatment. CONCLUSIONS: Prompt albumin therapy improves neurological function and blood-brain barrier integrity after acute intracortical hematoma. These observations have important potential clinical implications.

Albumins↗
PubMed2005

Semi-automated image processing system for micro- to macro-scale analysis of immunohistopathology: application to ischemic brain tissue.

Immunochemical staining techniques are commonly used to assess neuronal, astrocytic and microglial alterations in experimental neuroscience research, and in particular, are applied to tissues from animals subjected to ischemic stroke. Immunoreactivity of brain sections can be measured from digitized immunohistology slides so that quantitative assessment can be carried out by computer-assisted analysis. Conventional methods of analyzing immunohistology are based on image classification techniques applied to a specific anatomic location at high magnification. Such micro-scale localized image analysis limits one for further correlative studies with other imaging modalities on whole brain sections, which are of particular interest in experimental stroke research. This report presents a semi-automated image analysis method that performs convolution-based image classification on micro-scale images, extracts numerical data representing positive immunoreactivity from the processed micro-scale images and creates a corresponding quantitative macro-scale image. The present method utilizes several image-processing techniques to cope with variances in intensity distribution, as well as artifacts caused by light scattering or heterogeneity of antigen expression, which are commonly encountered in immunohistology. Micro-scale images are composed by a tiling function in a mosaic manner. Image classification is accomplished by the K-means clustering method at the relatively low-magnification micro-scale level in order to increase computation efficiency. The quantitative macro-scale image is suitable for correlative analysis with other imaging modalities. This method was applied to different immunostaining antibodies, such as endothelial barrier antigen (EBA), lectin, and glial fibrillary acidic protein (GFAP), on histology slides from animals subjected to middle cerebral artery occlusion by the intraluminal suture method. Reliability tests show that the results obtained from immunostained images at high magnification and relatively low magnification are virtually the same.

Antigen-Antibody Complex↗
PubMed2005

Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation.

Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. deltaPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted deltaPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced deltaPKC translocation and increased its cleavage at 3 h of reperfusion. Since deltaPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either deltaPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of deltaPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote deltaPKC translocation/cleavage.

Animals↗
PubMed2004

Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection.

BACKGROUND AND PURPOSE: High-dose human albumin therapy is strongly neuroprotective in models of brain ischemia and trauma and is currently being studied in a pilot-phase clinical stroke trial. Among its actions in ischemia, albumin induces the systemic mobilization of n-3 polyunsaturated fatty acids and may help to replenish polyunsaturated fatty acids lost from neural membranes. METHODS: We complexed 25% human albumin to docosahexaenoic acid (DHA; 22:6n-3) and compared its neuroprotective efficacy with that of native albumin in rats with 2-hour focal ischemia produced by intraluminal suture-occlusion of the middle cerebral artery. RESULTS: In animals treated with DHA-albumin, 0.63 g/kg, the improvement in neurobehavioral scores at 72 hours significantly exceeded that of other treatment groups, and the extent of histological protection (86% reduction in cortical infarction) was highly significant and tended to surpass the degree of cortical protection produced by native albumin at 1.25 g/kg (65%). DHA-albumin 0.63 g/kg, but not native albumin, also significantly reduced subcortical infarction and markedly diminished brain swelling. Lipidomic analysis of DHA-albumin-treated postischemic brains revealed a large accumulation of the neuroprotective DHA metabolite, 10,17S-docosatriene, in the ipsilateral hemisphere. CONCLUSIONS: The high-grade neuroprotection afforded by the DHA-albumin complex at relatively low albumin doses is clinically advantageous in that it might reduce the likelihood of acute intravascular volume overload and congestive heart failure sometimes induced when patients with compromised cardiovascular function are treated with high-dose albumin.

Animals↗
PubMed2004

Mild cardiopulmonary arrest promotes synaptic dysfunction in rat hippocampus.

Cardiac arrest (CA) patients exhibit learning and memory disabilities. These deficits suggest that synaptic dysfunction may underlie such disabilities. The hypothesis of the present study was that synaptic dysfunction occurs following CA and that this precedes cell death. To test this hypothesis, we used histopathological and electrophysiological markers in the hippocampus of rats subjected to CA. Evoked potentials (EP) were determined in the CA1 region of hippocampal slices harvested from animals subjected to CA or sham-operated rats by stimulating the Schaffer collaterals and recording in the CA1 pyramidal region. EP amplitudes were significantly attenuated by approximately 60% in hippocampal slices harvested from animals subjected to CA. Hippocampal slices harvested from sham rats exhibited normal long-term potentiation (LTP). In contrast, hippocampal slices harvested 24 h after CA exhibited no LTP response, even when no histopathological abnormalities were observed. These data suggest that synaptic dysfunction occurs before and without overt histopathology. We suggest that the synaptic dysfunction precedes and may be an early marker for delayed neuronal cell death in the hippocampus after CA.

Action Potentials↗
PubMed2004

Caffeinol confers cortical but not subcortical neuroprotection after transient focal cerebral ischemia in rats.

The combination of low-dose ethanol and caffeine (caffeinol) protects cortical areas of the brain from damage produced by distal focal ischemia in rats. There are no data, however, as to whether caffeinol influences injury in subcortical brain regions. Rats were anesthetized with halothane and subjected to 2 h of MCAo by poly-l-lysine-coated intraluminal suture. Caffeinol [a combination of ethanol, 0.33 g/kg, and caffeine, 10 mg/kg (n=5)] or vehicle (0.9% NaCl; n=7) was administered by i.v. infusion over a 2.5-h period beginning 15 min after reperfusion. Neurological status was evaluated daily, and histopathology was quantified at 3 days. Caffeinol therapy significantly improved the neurological score, reduced the total infarct volume (by 52%) and cortical infarct areas at multiple coronal levels, but subcortical infarction and brain swelling were not affected.

Animals↗
PubMed2004

Nuclear localization of the hypoxia-regulated pro-apoptotic protein BNIP3 after global brain ischemia in the rat hippocampus.

The 19 kD interacting protein 3, Nip3/BNIP3, is a pro-apoptotic member of the Bcl-2 family induced during hypoxia via the hypoxia-inducible factor (HIF) 1. BNIP3 has been linked to both apoptotic and necrotic cell death involving mitochondrial permeability transition. Since apoptotic and necrotic mechanisms may occur in brain ischemia, immunohistochemical changes of BNIP3 were studied at 1, 2, 3 and 7 days after transient global brain ischemia (12.5 min) in ventilated normothermic rats. In control brains, BNIP3-like immunoreactivity was moderately strong in neuronal processes or cytoplasm and absent in the nucleus. In the ischemia-vulnerable CA1 neurons, BNIP3-positive granules were seen in the nucleus at 1 and 2 days, and these neurons were damaged at 3 and 7 days. The resistant CA3 neurons showed nuclear BNIP3 labeling by 1 day and then returned to the normal state. BNIP3-positive granules did not overlap with the nucleolus. Constitutively expressed BNIP3 may participate in apoptotic and necrotic processes after brain ischemia. Nuclear location of BNIP3 after brain ischemia indicates a novel role for the regulation of cell survival in neurons or a general disturbance of the nuclear envelope.

Animals↗
PubMed2004

Delayed post-ischemic albumin treatment neither improves nor worsens the outcome of transient focal cerebral ischemia in rats.

Human albumin therapy within the first 4 h is highly neuroprotective in focal ischemia, but it is unknown whether delayed albumin therapy is deleterious. Rats received 2 h middle cerebral artery suture-occlusion. Human albumin (25%, 2.5 mg/kg; n=12) or vehicle (0.9% saline, 5 ml/kg; n=9) were administered at 19 h. Neurological status was evaluated daily, and histopathology and brain swelling were quantified at 3 days. Delayed albumin treatment, while ineffective, failed to show adverse effects.

Albumins↗
PubMed2004

Mitochondria consume energy and compromise cellular membrane potential by reversing ATP synthetase activity during focal ischemia in rats.

The direction of the chemical reaction of ATP synthetase is reversible. The present study was designed to determine whether mitochondria produce or consume ATP during ischemia. For this purpose, changes in mitochondrial membrane potential were measured in vivo at the site of a direct current (DC) electrode using a potentiometric dye, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and a rat model of focal ischemia. Two microL of dye (control group) or dye with oligomycin, an ATP synthetase inhibitor (oligomycin group), was injected into the parietotemporal cortex through the DC electrode. With the initiation of ischemia, a decrease in mitochondrial potential was observed within 20 seconds in the oligomycin group (earlier than the onset of DC deflection, P = 0.02). In contrast, in the control group, mitochondrial potential was maintained at 91 +/- 5% of the preischemia level for 118 +/- 38 seconds before showing full depolarization simultaneously with DC deflection. During the period of ischemia, the mitochondrial potential was higher in the control group (66 +/- 9%) than in the oligomycin group (46 +/- 8%, P = 0.0002), whereas DC potential was lower in the control group (-18 +/- 3) than in the oligomycin group (-15 +/- 2 mV, P = 0.04). These observations suggest that mitochondria consume ATP during ischemia by reversing ATP synthetase activity, which compromises cellular membrane potential by consuming ATP.

Adenosine Triphosphate↗
PubMed2003

Experimental intracerebral hemorrhage in the mouse: histological, behavioral, and hemodynamic characterization of a double-injection model.

BACKGROUND AND PURPOSE: A major limitation of intracerebral hemorrhage (ICH) research is the lack of reproducible animal models. The present study was conducted to validate in the mouse the double-injection method of ICH initially developed in the rat. We investigated the effect of intrastriatal injection of blood or cerebrospinal fluid (CSF) on cerebral blood flow (CBF), neurological score, hematoma volume, and brain swelling. METHODS: Male C57BL/6 mice were anesthetized with halothane/nitrous oxide delivered by face mask. Rectal and cranial temperatures were regulated at 37 degrees C to 37.5 degrees C. Mice were placed in a stereotactic frame, and a 30-gauge stainless steel cannula was introduced through a burr hole into the left striatum. Each mouse received a 5-microL injection of either whole blood or CSF (over 3 minutes), followed 7 minutes later by 10 microL injected over 5 minutes. The injection cannula was slowly withdrawn 10 minutes after the second injection. Control mice had only cannula insertion. CBF was studied by laser Doppler perfusion imaging. Neurological status was evaluated on days 1 and 2. After 2 days, hematoma volume and brain swelling were calculated. RESULTS: Physiological values were stable. Mice with ICH but not those with CSF or cannula alone had a marked, persistent neurological deficit and a highly reproducible hematoma, whose mean+/-SEM volume was 2.0+/-0.2 mm3 compared with a lesion size of 0.2+/-0.1 mm3 in mice with CSF. Residual swelling of the ipsilateral hemisphere at 48 hours was 5.7% in the hematoma and 1.5% in the CSF groups. Relative CBF in the neocortex ipsilateral to the injection site declined by approximately 45% to 60% during the first 20 minutes after cannula insertion/injection in all groups but began to renormalize at approximately 25 to 30 minutes in the CSF and cannula-only groups; in the hematoma group, cortical hypoperfusion of approximately 35% to 50% persisted during the 90-minute measurement period. CONCLUSIONS: The present ICH model in mice produces a consistent neurological deficit, hypoperfusion, hematoma volume, and brain swelling. This model closely mimics human hypertensive basal ganglionic ICH and should be useful for the evaluation of pharmaceutical therapies. Laser Doppler perfusion imaging is a useful new technique to quantify relative CBF changes and can be used for studies of dynamic changes of CBF in this in vivo model of ICH in mice.

Animals↗