This study investigates the mechanisms underlying handling-induced seizures in mice infected with Theiler's Murine Encephalomyelitis Virus. The research focuses on the role of activated microglia and astrocytes in modulating neuronal excitability and seizure activity.
Take a mouse injected with Theiler's Murine Encephalomyelitis Virus into the brain cortex.
The virus spreads to the hippocampus, where microglia and astrocytes recognize them and become activated.
The activated cells release pro-inflammatory cytokines, which block inhibitory neurotransmitter binding by triggering the internalization of their receptors while increasing excitatory neurotransmitter release.
The excess excitatory signal induces a continuous influx of positive ions, making neurons hyperexcitable.
To assess seizures due to external physical stimuli, called handling-induced seizures, ensure the absence of spontaneous seizures in the mouse with hyperexcitable neurons.
Slide a pen across the cage to create noise, then transfer the animal to another box and back, inducing stress.
If no seizures occur, provide more intense stress by flipping the mouse by its tail.
Stress triggers stress hormone release, further suppressing inhibitory signals while promoting excitatory signal-induced electrical discharges. This results in synchronized bursts of abnormal neuronal activity called seizures.
First, bring all the cages to the bench and observe the animals for seizures twice daily during the light phase. Score the seizure activity by a modified Racine scale and report the number and intensity of seizures. Next, slide a pen across the cage to make some noise and transfer each animal to another box and back. For animals that have not seized spontaneously or after gentle cage shaking, trigger seizures by more intense handling while carefully turning over the mouse by flipping it at its tail from left to right. Observe each animal for seizure behavior again and repeat the process for subsequent cages.
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