Biomedical subjects

Aneesh B Singhal

Publications and source records attributed to Aneesh B Singhal.

22 records · Page 2Linked to original sources

PubMed2002

Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke.

BACKGROUND: Hyperbaric oxygen therapy is considered an important stroke treatment strategy. BACKGROUND: To determine whether normobaric oxygen is neuroprotective, and, if so, what the therapeutic time window is. METHODS: Experiment 1-Serial diffusion- and perfusion-weighted MRI (DWI and PWI) was performed after middle cerebral artery filament occlusion (MCAO) in rats randomized to FiO(2) 30% (normoxia) or FiO(2) 100% (hyperoxia). Experiment 2-48-hour lesion volumes were analyzed in rats subjected to 2-hour MCAO and randomized to normoxia or hyperoxia starting 15, 30, or 45 minutes after MCAO and ending 15 minutes after reperfusion. RESULTS: Experiment 1-Lesion apparent diffusion coefficient (ADC) values were persistently low in normoxic animals. In hyperoxia-treated rats, ADC values in cortical border zones showed progressive recovery from 66 +/- 3% of contralateral before hyperoxia, to 104 +/- 20% at approximately 2 hours. Striatal ADC values showed early but ill-sustained improvement. ADC lesion volumes increased progressively in the normoxia group. In the hyperoxia group, ADC lesion volumes tended to decrease after starting hyperoxia; however, lesions later increased in size, and 2-hour lesion volumes were not significantly different from baseline. PWI showed stable right MCA hypoperfusion in all animals. Experiment 2-Hyperoxia within 30 minutes significantly reduced total and cortical lesion volumes at 48 hours after stroke. Striatal lesion volumes were significantly reduced in the hyperoxia-15 group. CONCLUSION: In rats subjected to transient stroke, 100% oxygen administered within 30 minutes salvages ischemic brain tissue, especially in the cerebral cortex. Reducing the time to treatment enhances the degree of neuroprotection.

Animals↗

PubMed2002

Mitogen-activated protein kinase inhibition in traumatic brain injury: in vitro and in vivo effects.

The authors provide the first in vitro and in vivo evidence that perturbations in mitogen-activated protein kinase (MAPK) signal-transduction pathways are involved in the pathophysiology of traumatic brain injury. In primary rat cortical cultures, mechanical trauma induced a rapid and selective phosphorylation of the extracellular signal-regulated kinase (ERK) and p38 kinase, whereas there was no detectable change in the c-jun N-terminal kinase (JNK) pathway. Treatment with PD98059, which inhibits MAPK/ERK 1/2, the upstream activator of ERK, significantly increased cell survival in vitro. The p38 kinase and JNK inhibitor SB203580 had no protective effect. Similar results were obtained in vivo using a controlled cortical impact model of traumatic injury in mouse brain. Rapid and selective upregulation occurred in ERK and p38 pathways with no detectable changes in JNK. Confocal immunohistochemistry showed that phospho-ERK colocalized with the neuronal nuclei marker but not the astrocytic marker glial fibrillary acidic protein. Inhibition of the ERK pathway with PD98059 resulted in a significant reduction of cortical lesion volumes 7 days after trauma. The p38 kinase and JNK inhibitor SB203580 had no detectable beneficial effect. These data indicate that critical perturbations in MAPK pathways mediate cerebral damage after acute injury, and further suggest that ERK is a novel therapeutic target in traumatic brain injury.

Animals↗

PubMed2002

Effects of normobaric hyperoxia in a rat model of focal cerebral ischemia-reperfusion.

Recent studies suggest that normobaric hyperoxia can be beneficial, if administered during transient stroke. However, increased oxygenation theoretically may increase oxygen free-radical injury, particularly during reperfusion. In the present study, the authors assessed the benefit and risks of hyperoxia during focal cerebral ischemia and reperfusion. Rats were subjected to hyperoxia (Fio2 100%) or normoxia (Fio2 30%) during 2-hour filament occlusion and 1-hour reperfusion of the middle cerebral artery. At 24 hours, the hyperoxia group showed 70% (total) and 92% (cortical) reduction in infarct volumes as compared to the normoxia group. Levels of oxidative stress were evaluated using three indirect methods. First, since oxygen free radicals increase blood-brain barrier (BBB) damage, Evan's blue dye extravasation was quantified to assess BBB damage. Second, the expression of heme oxygenase-1 (HO-1), a heat shock protein inducible by oxidative stress, was assessed using Western blot techniques. Third, an immunoblot technique ("OxyBlot") was used to assess levels of protein carbonyl formation as a marker of oxidative stress-induced protein denaturation. At 24 hours, Evan's blue dye extravasation per average lesion volume was similar between groups. There were no significant differences in HO-1 induction and protein carbonyl formation between groups, in the ipsilateral or contralateral hemispheres, at 6 hours and at 24 hours. These results indicate that hyperoxia treatment during focal cerebral ischemia-reperfusion is neuroprotective, and does not increase oxidative stress.

Animals↗

PubMed2002

Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Although infective endocarditis (IE) and nonbacterial thrombotic endocarditis (NBTE) are associated with cardioembolic stroke, differences in the nature of these conditions may result in differences in associated stroke patterns. We compared patterns of acute and recurrent ischemic stroke in IE and NBTE, using diffusion-weighted MRI (DWI). METHODS: Using ICD-9 diagnostic codes and medical record review, we identified 362 patients (387 episodes) with IE and 14 patients with NBTE. Thirty-five patients (with 27 episodes of IE, 9 NBTE) who underwent 36 initial and 29 follow-up DWI scans were selected for this study. DWI lesion size, number, and location were compared between groups and correlated with stroke syndromes and endocarditis features. RESULTS: DWI was abnormal in all but 2 patients. Four acute stroke patterns were identified: (1) single lesion, (2) territorial infarction, (3) disseminated punctate lesions, and (4) numerous small (<10 mm) and medium (10 to 30 mm) or large (>30 mm) lesions in multiple territories. All patients with NBTE exhibited pattern 4, whereas those with IE exhibited patterns 1, 2, 3, and 4 (6, 2, 8 and 9 episodes, respectively). Seventy-five percent of patients with pattern 3 exhibited the clinical syndrome of embolic encephalopathy. Vegetation size, valve, and organisms had no correlation with stroke patterns. CONCLUSION: DWI has utility in differentiating between IE and NBTE. Patients with NBTE uniformly have multiple, widely distributed, small and large strokes, whereas patients with IE exhibit a panoply of stroke patterns.

Acute Disease↗