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Biomedical subjects

Andrew J Cole

Publications and source records attributed to Andrew J Cole.

6 recordsLinked to original sources

Diffusion-weighted imaging abnormalities in the splenium after seizures.

PURPOSE: Transient increased T2 signal in the splenium of the corpus callosum after seizures has been reported and sometimes attributed to a postulated toxicity of anticonvulsant medications (AEDs). METHODS: We describe two patients with bitemporal epilepsy. RESULTS: Transiently increased T2 signal (in one) and decreased apparent diffusion coefficient (ADC) (in both) in the splenium appeared to be related directly to acute seizures. CONCLUSIONS: These cases illustrate an unusual acute postictal imaging finding, highlight involvement of an important commissural pathway, and suggest that seizures per se, and not their treatment, are the cause of transient white-matter abnormalities in these cases.

Acute Disease↗

Phosphorylation of P42/P44 MAP kinase and DNA fragmentation in the rat perforant pathway stimulation model of limbic epilepsy.

The intracellular signaling pathways associated with neuronal injury after perforant pathway stimulation of the rodent hippocampus have not been examined. To determine whether activation of the p42/p44 (Erk1/2) MAP kinase (MAPK) phosphorylation cascade is linked to neuronal injury after perforant pathway stimulation (PPS), we stained for phosphorylated Erk1/2 (P-Erk1/2) and for DNA fragmentation, a marker of cell death after PPS. Eighteen Sprague-Dawley rats underwent PPS for 6 (n=6), 12 (n=6), or 24 (n=6) h and were sacrificed either immediately (n=9) or 48 h (n=9) after stimulation. Sham-operated non-stimulated control animals (n=2) and control animals receiving low frequency stimulation only (n=4) were also examined. Brain sections were stained for DNA fragmentation and P-Erk1/2. DNA fragmentation was evident only in granule cells and CA3 pyramidal cells of the stimulated side 48 h after 24 h of PPS. PPS resulted in robust phosphorylation of Erk1/2 that displayed a stereotyped timecourse, appearing first in hilar neurons on the ipsilateral side and later in hilar neurons, granule cells, hippocampal pyramidal and non-neuronal cell populations on both the stimulated and contralateral sides. Both Erk1/2 phosphorylation and DNA fragmentation show definite and reproducible staining patterns after PPS that vary based on duration of stimulation. Populations displaying Erk1/2 activation appeared to differ from those showing DNA fragmentation and neuronal injury.

Animals↗

Are seizures harmful: what can we learn from animal models?

Epilepsy is a brain disease that requires distributed neuronal networks for its expression. Several characteristics of epilepsy, including its natural history, the latency between an initial insult and the first manifestation of seizures, the complex interaction of seizures with development as a function of developmental stage, the modulating effect of systemic physiological responses, and the fact that seizures are ultimately defined by a combination of electrical and behavioral criteria all suggest that epilepsy should ideally be studied in an intact whole animal preparation. Such preparations offer the ability to study acute and chronic changes in brain structure and function after single or repeated seizures. Animal models have major limitations, however, including strain specificity, difficulty in isolating potentially confounding variables, a relative lack of accessible higher cortical functions, such as language and abstract processing, and shorter lifespans that may be insufficient to allow the complete expression of seizure-related injury. Information we have learned from animal studies includes a broad understanding of the chemical, molecular and anatomic consequences of seizures, including their temporal and spatial relationships to each other, and information on the consequences of seizures as a function of development. Recent studies have cast light on potential mechanisms of resistance to seizure-induced injury in the developing brain. In the future, we can anticipate that animal models will continue to be useful, especially when whole-animal preparations are used to generate material for detailed in vitro examination.

Animals↗