Role of Cortical Spreading Depressions for Secondary Brain Damage after Traumatic Brain Injury in Mice

Abstract

In recent years, several studies have unequivocally shown the occurrence of cortical spreading depressions (CSDs) after stroke and traumatic brain injury (TBI) in humans. The fundamental question, however, is whether CSDs cause or result from secondary brain damage. The aim of the current study was, therefore, to investigate the role of CSDs for secondary brain damage in an experimental model of TBI. C57/BL6 mice were traumatized by controlled cortical impact. Immediately after trauma, each animal showed one heterogeneous direct current (DC) potential shift accompanied by a profound depression of electroencephalogram (EEG) amplitude, and a temporary decrease of ipsi-and contralateral regional cerebral blood flow (rCBF) suggesting bilateral CSDs. Within the next 3 h after TBI, CSDs occurred at a low frequency (0.38 CSD/h per animal, n = 7) and were accompanied by rCBF changes confined to the ipsilateral hemisphere. No significant relationship between the number of SDs and lesion size or intracranial pressure (ICP) could be detected. Even increasing the number of posttraumatic CSDs by application of KCl by more than six times did not increase ICP or contusion volume. We therefore conclude that CSDs may not contribute to posttraumatic secondary brain damage in the normally perfused and oxygenated brain.

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

“…In most rodent models of cerebral contusion, only a single CSD is triggered by the initial mechanical insult, which is followed by few or no subsequent CSD waves in the ensuing hours (Ozawa et al, 1991;Nilsson et al, 1993). To determine whether CSD contributes to the maturation of cortical contusions in normally perfused and oxygenated animals, Baumgarten et al (2008) applied an approach used earlier by others in experimental stroke: they elicited additional CSDs, remote and independent from the primary injury, which then invaded the evolving contusion. There was no effect of these additional CSDs on injury volume at 24 hours, although secondary insults were specifically (and in one sense, commendably) minimized in this study.…”

The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

“…62 The processes that allow for persistence of this depression beyond a few hours are unknown; however, given the known link between CSD and cortical plasticity, 64 it seems likely that synaptic events such as long-term depression may be important. Cortical waves of depression have been monitored after injury induced with predominantly focal injury models, such as the LFPI, [65][66][67][68] Feeney's weight drop, 69 and the controlled cortical impact (CCI) model, 70 but have yet to be documented after a diffuse model of injury, such as the WDIA model. Nevertheless, our findings suggest that CSD is likely to be an important phenomenon after both diffuse and focal forms of injury, and may be important in establishing persistent cortical cellular changes.…”

Inhaled Nitric Oxide Reduces Secondary Brain Damage after Traumatic Brain Injury in Mice

“…Regional cerebral blood flow (rCBF) was measured by Laser Doppler Fluxmetry (Periflux 4001 Master, Perimed, Stockholm, Sweden) as previously described. [9][10][11] Intracranial pressure (ICP) was measured by an intraparenchymal probe (Mammendorfer Institut, Mammendorf, Germany) placed 2 mm right of the bregma. Blood samples (50 ml) were collected before trauma and at the end of the observation period for blood gas analysis.…”