Characterizing Spatiotemporal Evolution Of Cortical Spreading Depression In Rats By Optical Imaging

Cortical spreading depression (CSD) is an important neurophysiological phenomenon correlating with some neural disorders, such as migraine, cerebral ischemia and epilepsy. By now, we are still not clear about the mechanisms of CSD's initiation and propagation, also the relevance between CSD and those neural diseases. Nevertheless, characterization of CSD, especially the spatiotemporal evolution, will promote the understanding of the CSD's nature and mechanisms. Many techniques have been taken into the research of CSD, including electrophysiological recordings, histochemistry, and magnetic resonance imaging (MRI). However, they may have some limitations from the invasive property and the insufficient resolution in spatial or temporal dimension. Optical intrinsic signal imaging (OISI) can measure the reflectance in a large region of the cortex continuously with tens of millisecond temporal and microns spatial resolution. So it is a suitable neuroimaging technique to sduty the spatiotemporal evolution of CSD.In this dissertation, the OISI at 550 nm based on changes of reginonal cerebral blood volume (CBV) is used to observe the spatiotemporal evolution of CSD in rats in vivo. The spatiotemporal characteristics of CSD under KCl and pinprick stimulation, normal blood perfused and focal cerebral ischemia are compared. In the current study, the results have shown that: a series of successive CSDs are time-varying; the spontaneous CSD during focal cerebral ischemia is spatiality-varying. The new finding is an important supplement and revision to the traditional notion that considers CSD is an"all or none"process. The overall results and review of our study are listed as following:1) By combining OISI and electrophysiology recording, the quantity correlation between optical and electrical signal during CSD is analyzed. The optical signal from the surrounding area of electrode has tight correlation with the DC potential change: the initial two phases of optical signals coincide well with the negative deflection of direct current (DC) potential. Although the timing of the third phase of optical signals primarily reflecting the increase of CBV is lagged to the DC potential shift, the amplitudes of them show a significant linear correlation (R=0.96). This basic work indicates the neurovascular coupling during CSD which form the basis for the separate OISI to detect CSD.2) OISI has been applied to monitor CSD in biparietal cortex for the first time. The paradigm thus constitutes a self-comparison model for quantitative assessment of optical recording. In fact, the imaging system in current study has a good signal to noise ratio (SNR) over 10. The results show the optical signals of CSD in both hemispheres have unilateral, symmetrical and independent properties. Regardless of the stimuli of pinprick and KCl, the properties of evoked CSD are essentially similar. And the reflectance changes during each CSD event are surely profiled by the four phases: decrease, increase, decrease and increase. The results implicate the initiation and propagation of CSD might involve the volume transmission mechanism by K+ diffusion.3) OISI has been used to observe a series of successive CSD waves induced by K+/pinprick. Except for the first CSD wave, the following waves don't spread fully in the observed cortex all the time and they might abort in the medial area. Independent on the stimulation of pinprick or KCl, a short interval of the current CSD to the last CSD no more than 4 min would induce the current CSD be partially propagated. For the first time, the data reveals the time-varying propagation patterns of CSD waves might be affected by the interval between CSD waves.4) In the focal cerebral ischemia rats induced by middle cerebral artery occlusion (MCAO), a series of spontaneous CSD waves are observed by OISI for the fisrt time. Optical reflectance signals during CSD present three types of regional variation significantly: flat, increase and decrease. These changes are corresponding to infarct area, penumbra and normal area. With the reoccurrence of spontaneous CSDs, the origins migrate in the ipsilateral hemisphere with a general trend towards the medial cortex. The uninvaded area of CSD in the lateral is enlarging, the penumbra is attenuating but the infarct is expanding. OISI suggests that the spatiotemporal characteristics of spontaneous CSD waves reveal the dynamic evolution of focal cerebral ischemia.