Release of Excitatory Amino Acids in the Penumbra of a Focal Cortical Necrosis

Abstract

A cortical tissue necrosis from focal trauma expands between 30% and 300% from its initial size within 24 h, depending on the species studied. To shed light on the pathophysiological processes in the penumbra 1 zone after a focal cortical lesion, the release of excitatory amino acids into the traumatic penumbra zone 1 was measured throughout the entire period of necrosis expansion. A microdialysis probe was inserted at an oblique angle into the cortex of Sprague-Dawley rats 2 mm below the brain surface. One day later, a highly standardized cortical freezing lesion was induced at the brain cortex above the microdialysis probe. Dialysate was continuously collected prior to, during, and up to 24 h after trauma and analyzed for primary amino acids. In each animal, it was confirmed histologically that the tip of the microdialysis probe was localized in the gray matter in close proximity to the primary lesion. Following induction of the trauma, a statistically significant sharp increase of the dialysate level of aspartate, glutamate, glycine, and serine was observed. Thereafter, the dialysate levels of these amino acids returned to baseline levels without any further increase throughout the remaining observation period. This process ranged in time from a few minutes to a few hours. The level of alanine in the dialysate was essentially not altered throughout the experiment. Although the early post-traumatic increase of the excitatory neurotransmitters aspartate and glutamate may well contribute to the secondary lesion growth of a cortical necrosis after trauma, glutamate receptor targeted therapeutic intervention may be in view of these findings of limited use when initiated post trauma.

The Neuroprotective Effects of Oxaloacetate in Closed Head Injury in Rats is Mediated by its Blood Glutamate Scavenging Activity

“…The time point of 90 minute after CHI was chosen because previous studies have demonstrated that the excess glutamate concentration in brain fluids in the rat model of CHI reaches a peak after about 1 hour. 12,13,29,30 MAP, HR, arterial blood gas tensions, and Hb concentrations were assessed at 0, 60, 90, and 120 minutes after closed head injury. The MAP was lower in the maleate group compared with the saline treatment group at 90 minutes (P<0.05).…”

Neuronal gap junction coupling as the primary determinant of the extent of glutamate-mediated excitotoxicity

“…The surrounding neural tissue suffers from the secondary effects characterized by apoptosis (Guyot et al 2001; Stoffel et al 2002). A critical determinant of cell death in the penumbra is thought to be excessive release of glutamate from injured cells and the attendant glutamate-dependent excitotoxicity of “bystander” cells (Arundine and Tymianski 2004; Choi 1988; Hazell 2007).…”

Effects of Blood Glutamate Scavenging on Cortical Evoked Potentials

“…Nowadays, it is well accepted that abnormally high Glu levels in brain interstitial and cerebrospinal fluids are the hallmark of several neurodegenerative conditions, such as stroke and, traumatic brain injury (Castillo et al 1996;Johnston et al 2001;Stoffel et al 2002;Suzuki et al 2002). As excess Glu exerts neurotoxic properties, a great deal of efforts has been made in recent years to reach a better understanding of how the brain protects itself from excess Glu, and on ways drugs could provide neuroprotection.…”