Small damage of brain parenchyma reliably triggers spreading depolarization

Objectives: Spreading depolarization (SD) is a well-recognized component of the stress response of the cortex to its acute injury. Cortical SD has been shown to occur in severe brain insults and standard neurosurgical procedures in patients and is supposed to promote delayed secondary brain injuries. Stereotactic surgery and site-specific intracerebral microinjections produce a small tissue injury when a thin needle is inserted directly into the brain parenchyma (via the cannula guide). The present study was designed to examine whether such a parenchymal damage can trigger SD. Methods: Experiments were performed in awake freely moving rats with simultaneous video-monitoring of behavior and recording of SD-related DC potentials in the cortex and striatum. A parenchymal damage was produced by 1-mm protruding of thin (0.3-mm diameter) cannula beyond the tip of cannula guide preliminary implanted into the amygdala or deep cortical layers. Results: We found that the micro-injury of the brain parenchyma the volume of which did not exceed 0.3 mm(3) was sufficient to initiate SD in a very high proportion of rats (75-100%). The amygdala showed increased resistance against the injury-induced SD compared to the cortex. We further showed that SD triggered by the local micro-injury invaded remote intact regions of the cortico-striatal system and evoked specific changes in spontaneous animal behavior. Discussion: The findings indicate that SD may represent a previously unidentified side effect of local parenchymal injury during site-specific microinjections and stereotactic surgery.