Region-Specific Vulnerability of the Amygdala to Injury-Induced Spreading Depolarization

Abstract

Spreading depolarization (SD), a self-propagated wave of transient depolarization, regularly occurs in the cortex after acute brain insults and is now referred as an important diagnostic and therapeutic target in patients with acute brain injury. Here, we show that the amygdala, the limbic structure responsible for post-injury neuropsychological symptoms, exhibits strong regional heterogeneity in vulnerability to SD with high susceptibility of its basolateral (BLA) region and resilience of its centromedial (CMA) region to triggering SD by acute focal damage. The BLA micro-injury elicited SD twice as often compared with identical injury of the CMA region (71% vs. 33%). Spatiotemporal features of SDs triggered in the amygdala indicated diverse patterns of the SD propagation to the cortex. Our results suggest that even relatively small cerebral structures can exhibit regional gradients in their susceptibility to SD and the heterogeneity may contribute to the generation of complex SD patterns in the injured brain.

Different vulnerability of fast and slow cortical oscillations to suppressive effect of spreading depolarization: state-dependent features potentially relevant to pathogenesis of migraine aura

“…S 1 ). As reported previously [ 21 ], the local injury of the amygdala triggered SD with about 60% probability. In the present study, we analyzed recordings obtained in rats with histologically verified damaging the basolateral amygdala (BLA) that exhibited maximal susceptibility to SD [ 20 , 21 ].…”

“…As reported previously [ 21 ], the local injury of the amygdala triggered SD with about 60% probability. In the present study, we analyzed recordings obtained in rats with histologically verified damaging the basolateral amygdala (BLA) that exhibited maximal susceptibility to SD [ 20 , 21 ]. At a week interval, the BLA pinprick induced SD with similar probability in test 1 (59%, 19/32) and test 2 (72%, 23/32) in awake rats ( p = 0.43, Fisher exact test) and reduced probability (19%, 6/32 in test 3) in anesthetized rats ( p < 0.001).…”

“…Experiments started two weeks after the surgery.In each rat,three tests with a week interval were performed – the first and second tests under wakefulness and the third test after introduction of urethan anesthesia (1.5 mg/kg, i.p.). In each test, rats were individually placed in a shielded chamber and the implanted connector was attached to the recording cable and spontaneous cortical activity was recorded before (baseline) and after bilateral pinprick of the amygdala as described previously [ 18 , 21 ]. Briefly, the needle was inserted into the guide cannulaand extended 1.0 mm from its tip, thus providing a small standard damage of the neuronal tissue (Supplementary Fig.…”

“…Migraine aura/SD occurs in the undamaged cortex of migraine patients while most experimental approaches of SD induction include direct mechanical or chemical stimulation of the cortex. To exclude potential confounding effects of direct cortical stimulation on cortical activity [ 19 ], we initiated SD extracortically –by a pinprick of the amygdala connected with the cortex by a gray matter bridge allowing slow non-synaptic propagation of SD [ 18 , 20 , 21 ]. SD induced in the amygdala cannot reach the cortex via direct pathway because SD is unable to cross the thick layer of myelinated fibers separating the cortex from subcortical structures.…”