A Rat Model Of Somatosensory-Evoked Reflex Seizures Induced By Peripheral Stimulation

Abstract

ObjectiveWe introduce a novel animal model of somatosensory stimulation-induced reflex seizures which generates focal seizures without causing damage to the brain.\n\nMethodsSpecifically, we electrically stimulated digits or forepaws of adult rats sedated with dexmedetomidine while imaging cerebral blood volume and recording neurophysiological activity in cortical area S1FL. For the recordings, we either inserted a linear probe into the D3 digit representation or we performed surface electrocorticography (ECoG) recordings.\n\nResultsPeripheral stimulation of a digit or the forepaw elicited seizures that were followed by a refractory period with decreased neuronal activity, or another seizure or a normal response. LFP amplitudes in response to electrical pulses during the seizures (0.28 {+/-} 0.03 mV) were higher than during normal evoked responses (0.25 {+/-} 0.05 mV) and refractory periods (0.2 {+/-} 0.08 mV). Seizures generated during the stimulation period showed prolonged after-discharges that were sustained for 20.9{+/-}1.9 s following the cessation of the stimulus. High-frequency oscillations were observed prior to and during the seizures, with amplitudes higher than those associated with normal evoked responses. The seizures were initially focal. Optical imaging of the cerebral blood volume response showed that they propagated from the onset zone to adjacent cortical areas, beyond the S1FL representation of the stimulated digit or forepaw. The spatial extent during seizures was on average 1.74 times larger during the stimulation and 4.1 times following its cessation relative to normal evoked responses. Seizures were recorded not only by probes inserted into cortex but also with ECoG arrays (24.1{+/-}5.8 seizures per rat) placed over the dura matter, indicating that the seizures were not induced by damage caused by inserting the probes to cortex. Stimulation of the forepaw elicited more seizures (18.8{+/-}8.5 seizures per rat) than stimulation of a digit (1.7{+/-}0.7). Unlike rats sedated with dexmedetomidine, rats anesthetized with urethane showed no seizures, indicating that the seizures may depend on the use of the mild sedative dexmedetomidine.\n\nSignificanceOur proposed animal model generates seizures induced by electrical sensory stimulation free of artifacts and brain damage. It can be used for studying the mechanisms underlying the generation and propagation of reflex seizures and for evaluating antiepileptic drugs.\n\nHIGHLIGHTSO_LIPeripheral stimulation of the rat forepaw or digits induces seizures\nC_LIO_LISeizures are evoked with no direct application of convulsants, electro-stimulation or damage to the brain\nC_LIO_LISeizures are focal at onset, then spread beyond the spatial representation of the digit or forepaw\nC_LIO_LISeizures persist following the cessation of the stimulus\nC_LIO_LIProposed animal model may support the study of reflex seizures and improving therapeutic interventions\nC_LI