Type 2 Diabetes Mellitus Exacerbates Brain Injury After Status Epilepticus in Rats

TL;DR

This study shows that Type 2 Diabetes in rats leads to worse brain damage after a severe seizure condition called status epilepticus.

Contribution

The study reveals a novel link between Type 2 Diabetes and increased brain injury following status epilepticus in rats.

Findings

T2DM rats had higher seizure severity and delayed onset of severe seizures compared to controls.

T2DM rats showed increased brain cell death and tissue loss after seizures.

T2DM rats had increased microglia density but reduced glial cells following seizures.

Abstract

Background: Clinical and experimental evidence suggests comorbidity between diabetes mellitus (DM) and epilepsy, including a higher incidence of status epilepticus (SE). However, the association between Type 2 Diabetes Mellitus (T2DM) and epilepsy is not fully understood. Therefore, this study aimed to analyze the severity of SE and the consequent brain injury in male Wistar rats with T2DM. Methods: To induce T2DM, postnatal day (P) 3 rats were injected with streptozocin (STZ, 100 mg/kg, s.c.; n = 18); control rats received an equal volume of citrate buffer (pH 4.5) used as vehicle (n = 16). Glycemia was monitored at P30, P40, P60, and P90 in both experimental groups. Subsequently, rats were injected intraperitoneally with lithium chloride (LiCl, 3 mEq/kg, i.p.), and 18 h later, at P90, SE was induced by pilocarpine hydrochloride (30 mg/kg, s.c.). Matched control rats were injected with LiCl and physiological saline solution. The severity of SE, the neurodegeneration, cell and tissue loss, and microglia and glial responses were evaluated in the hippocampus, amygdala, thalamus, the piriform cortex. Results: Hyperglycemia was evident at P90 in STZ rats compared with vehicle (p < 0.05). T2DM rats had a higher frequency of stage V seizures and increased latency to the first stage V seizure and to SE compared with control rats (p < 0.05). T2DM rats showed an increased number of Fluoro-Jade B-positive cells, a reduction in cell density, and tissue loss, associated with an increased microglia density but a reduced glial cell count after SE (p < 0.05). Conclusions: Our findings suggest that T2DM is associated with greater seizure severity and increased brain injury following SE.

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