Biomedical subjects

André Obenaus

Publications and source records attributed to André Obenaus.

5 recordsLinked to original sources

PubMed2005

Neuroprotection from soman-induced seizures in the rodent: evaluation with diffusion- and T2-weighted magnetic resonance imaging.

Exposure to the organophosphate nerve agent soman produces seizures that in turn lead to neuropathology. This study describes the temporal and spatial evolution of brain pathology following soman-induced convulsions and the attenuation of these alterations after neuroprotective intervention with magnetic resonance imaging (MRI). Neuroimaging 12 h after soman exposure, the hippocampus and thalamus exhibited significant decreases (23%) in apparent diffusion coefficients (ADC). These acute effects were resolved by 7 days. In addition, T2 measurements declined significantly at 12 h (37%) returning to near normal values by 24 h. Histopathological analyses confirmed moderate cell loss within the hippocampus and piriform cortex. Together these findings suggest that initial cell death was resolved through regional cellular remodeling. Pharmacological countermeasures were administered in the form of diazepam, a benzodiazepine anticonvulsant, or gacyclidine (GK-11), an anti-glutamatergic compound. Diazepam therapy applied immediately after soman exposure prevented acute ADC changes. However the presence of edema, using T2 measurements, was detected at 3 h within the retrosplenial, amygdala and piriform cortices and at 12 h in the thalamus (34% below normal). GK-11 therapy appeared to prevent most of these changes. However at 7 days after soman, a decrease (17%) in ADC was observed in the piriform cortex. Pathology was confined to the piriform cortex suggesting that this region is more difficult to protect. This is the first report that provides temporal and spatial resolution using MRI with histological correlation of pharmacological interventions against soman-mediated seizure-induced neuropathology.

Animals↗

PubMed2005

Cell-permeant calcium buffer induced neuroprotection after cortical devascularization.

An excitotoxic cascade resulting in a significant intracellular calcium load is thought to be a primary mechanism leading to neuronal death after ischemia. One way to protect neurons from injury is through the use of cell-permeant calcium buffers. These molecules have been reported to be neuroprotective via their ability to increase the cell's overall Ca(2+) buffering load as well as by attenuating neurotransmitter release. However, their efficacy when given after injury has yet to be determined. We used diffusion-weighted magnetic resonance imaging (DWI), histological, and immunohistochemical methods to determine the neuroprotective efficacy of 2-aminophenol-N, N, O-triacetic acid acetoxymethyl ester (APTRA-AM) after focal cerebral ischemia. Injured animals were given two injections of APTRA-AM at 1 and 12 h after injury. Animals were imaged prior to injury and then at 12, 24, 48 h and 3 and 7 days after injury. After 7 days the animals were euthanized for correlative cresyl violet histology and immunohistochemistry. Injury resulted in a decrease in the apparent diffusion coefficient (ADC) of the injured area within the first 12 h of injury, which returned to normal by 7 days. In contrast, animals injected with APTRA-AM showed no significant change in the ADC at any time point studied. Tissue analysis showed that APTRA-AM significantly reduced the infarct size by 85% and extent of inflammatory cell infiltration by 94%. The results clearly demonstrate significant neuroprotection by APTRA-AM when given after injury.

Animals↗

PubMed2004

Neuronal and glial cell populations in the piriform cortex distinguished by using an approximation of q-space imaging after status epilepticus.

BACKGROUND AND PURPOSE: Temporal lobe epilepsy produces an injury cascade that includes neuronal loss and gliosis. The pilocarpine model reliably reproduces the symptoms of temporal lobe epilepsy and the resulting neuronal glial changes can be accurately depicted on diffusion-weighted images. The judicious choice of diffusion-encoding gradients can isolate multiple apparently isochromatic diffusing populations, but the assignment of these populations to specific tissue characteristics has been difficult. We sought to distinguish neuronal tissue from glial cell-infiltrated tissue by using signatures from unique spin populations obtained from an approximation of q-space imaging. METHODS: Ten male Sprague-Dawley rats received pilocarpine injections to induce seizures. All animals underwent diffusion-weighted imaging at 12 hours, 24 hours, and 7 days. At least two animals were selected for histologic analysis at each imaging time point. RESULTS: The results indicated that seizure-induced neurologic dysfunction may have been reflected in the emergence of new spin populations. In the piriform cortex-amygdala region of interest, the mean free diffusion path increased from 12 to 20 microm within 12 hours of seizure onset and persisted for at least 7 days. These results were temporally correlated with histologic evidence of necrotic changes. CONCLUSION: Our results suggest that even incomplete sampling of q space can provide useful physiologic information.

Amygdala↗

PubMed2003

Recurrent nonstatus generalized seizures alter the developing chicken brain.

PURPOSE: Noninvasive magnetic resonance imaging was used to assess the evolution of seizure-induced pathology in epileptic, carrier, and normal chickens. Our objective was to determine whether repetitively evoked seizures in an epileptic fowl model of generalized seizures resulted in altered brain development. METHODS: Data were obtained from seizure and control groups at 45, 90, and 180 days after hatching. RESULTS: At 180 days, apparent diffusion coefficient (ADC) values in the optic tectum and archistriatum of the stimulated epileptic chicks were reduced, whereas ADC values in the nonstimulated group remained unchanged. The mean brain volume of epileptic chickens from the stimulated group was smaller than that from the nonstimulated group at 90 and 180 days. CONCLUSIONS: These findings establish that recurrent seizures modify the brain matrix.

Age Factors↗

PubMed2002

Evolution of beta-amyloid induced neuropathology: magnetic resonance imaging and anatomical comparisons in the rodent hippocampus.

Alzheimer's disease (AD) is characterized by the anatomical appearance of beta-amyloid (betaA) plaques and neurofibrillary tangles. These changes are also associated with cyclical inflammation, oxidative damage and, as inferred from the autopsied brains of patients, progressive injury to neurons. Here, we report the short-term effects of an intrahippocampal injection of the toxic betaA peptide fragment 25-35 in rats using quantitative magnetic resonance imaging (MRI) methods. Physiological changes within the cornu ammonis 1 (CA1) region of the hippocampus were monitored using a 1.5 T scanner at time points of 0.25, 1 and 24 h, and 7 and 14 days post injection. Spin echo T2-weighted (T2W) and diffusion weighted (DW) images were sequentially acquired. Apparent diffusion coefficients (ADC) were calculated and compared with histological alterations. A significant elevation in mean ADC values (17%) was observed in the ipsilateral CA1 at 14 days. The ADC changes were associated with disrupted pyramidal cells and nuclear lysis observed in histological sections. The contralateral CA1 exhibited a significant decrease in mean ADC of 15% at 14 days post treatment. Histological changes in the contralateral hippocampus suggested decreased neuronal density. T2W maps revealed no significant differences between the active betaA 25-35 fragment and its non-active analog, betaA 35-25. In conclusion, these results, based on changes in hippocampal ADC, demonstrate that the betaA 25-35 treatment induced pathology consistent with edema and cellular necrosis. This is the first report describing the evolution of AD-like pathology in an animal model using DW imaging.

Alzheimer Disease↗