Post-stroke neural activities using electrocorticogram (ECoG) in a rat model of focal ischemia

Abstract

An ischemic stroke lesion consists of ischemic core and penumbra. In the ischemic core, the neurons are damaged permanently because blood flow is reduced to a very low level. In the penumbra around the infarct core, the neurons are functionally impaired but structurally preserved. The structural and functional reorganization in penumbra facilitates recovery after stroke. However, delayed ischemia continues to develop in penumbra after the initial ischemia, and neuron survival in the penumbra is time-limited. Monitoring the ischemic penumbra is important for patient screening, treatment and prediction of recovery. MRI has made the visualization of the penumbra possible; however, MRI does not reliably detect damage in the first hours after stroke, and even may be misleading in some stroke cases. Consequently, the patients would miss the time window for effective therapeutic intervention. Moreover, MRI is costly and could only be performed for limited number of times per day. As an alternative, electrocorticogram (ECoG) provides a direct, convenient brain monitoring method by recording the electrical signals from surface of the cortex. However, the application of ECoG in experimental brain ischemia is not well studied. The objective of this study is to investigate the ECoG activities in a rat model of focal ischemia from the acute phase to the chronic phase. In this study, focal cerebral ischemia was induced by intraluminal suture middle cerebral artery occlusion (MCAo), which produces a penumbra in sensorimotor cortex. Infarct maturation process and location of penumbra were revealed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Throughout the acute phase (after 3 and 6 hours), subacute phase (after 24, 48 and 72 hours) and chronic phase (after 96, 120, 144 and 168 hours), ECoG data were recorded from the bilateral sensorimotor cortex using stainless steel electrodes. The autoregressive model was applied to estimate the ECoG power spectrum density. The alpha-to-delta ratio (ADR), a quantitative ECoG parameter, was calculated from the ratio between the alpha power (8-13Hz) and the delta power (1-4Hz). Moreover, peak power variability was also calculated from ECoG recordings. The sensorimotor function and motor coordination were measured by De Ryck's test and beam walking test respectively. The results from ECoG recordings showed suppression of ECoG amplitude in the penumbra during MCAo. ECoG power spectral analysis showed dominant delta activities in the acute phase and suppression of alpha/beta activities in the subacute phase, which possibly indicated striatum ischemia and delayed cortical ischemia at different stroke phases. Quantitative ECoG analysis showed the alpha/beta variability decreased during subacute phase and fully recovered in the chronic phase. ADRs were below 50% of the pre-stroke level at both acute and subacute phases, and the improvement in ADRs was highly correlated with sensorimotor function recovery (Pearson’s correlation, r = 0.9895, p<0.05). In addition, TTC stained brain slices confirmed that striatum infarct completed within 24 hours and the cortical infarct expanded until 72 hours. Altogether, this study demonstrated that ECoG provided information on the stroke pathophysiology in a rat model of focal ischemia from acute phase to chronic phase. Post-stroke functional recovery was closely related to the restoration of neural activity in the penumbra. Quantitative ECoG parameters, such as ADR and peak power variability, have the potential to be used in stroke diagnosis and prognosis.