Role of Excitatory Amino Acid‐Mediated Ionic Fluxes in Traumatic Brain Injury

Abstract

One major event taking place at the moment of traumatic brain injury in neuronal cells is the occurrence of massive ionic fluxes across the plasma membrane, which can be referred to as traumatic depolarization (TD). Unlike spreading depression, TD can occur over wide brain areas simultaneously. Furthermore, recovery from TD often takes far longer than recovery from ionic perturbation elicited by the passage of a single wave of spreading depression. Neuronal cell damage caused by ischemic brain injury is also initiated by massive ionic fluxes, termed anoxic depolarization. The occurrence of similar ionic events in these two forms of brain injury may account for the genesis of diffuse ischemia-like damage without actual episodes of hypoxia or ischemia in traumatic brain injury. We review the data indicating that excitatory amino acids (EAA) may play a vital role in producing TD, and that such EAA-mediated ionic perturbation is responsible for a number of posttraumatic events including subcellular metabolic dysfunction and cellular responses such as microglial activation and astrocytic transformation. TD may represent one of the most important mechanisms of diffuse neuronal cell dysfunction and damage associated with traumatic brain injury.

Metabolic and Histologic Effects of Sodium Pyruvate Treatment in the Rat after Cortical Contusion Injury

“…TBI-induced glutamate release and ionic fluxes (Faden et al, 1989;Katayama et al, 1990Katayama et al, , 1995Yoshino et al, 1992;Fineman et al, 1993;Palmer et al, 1993;Rose et al, 2002) initiate increased metabolic demands, reflected in early, transient increases in cerebral metabolic rates for glucose (Sunami et al, 1989b;Yoshino et al, 1991;Kawamata et al, 1992;Sutton et al, 1994;Lee et al, 1999) and increased anaerobic glycolysis, reflected by an increase in extracellular and tissue lactate levels Dhillon et al, 1997;Bartnik et al, 2005Bartnik et al, , 2007b. TBI is also known to induce mitochondrial dysfunction (Vink et al, 1990;Verweij et al, 1997;Xiong et al, 1997), increase free radical production and oxidative stress (Hall et al, 1993(Hall et al, , 2004Marklund et al, 2001;Tavazzi et al, 2005), induce zinc release and accumulation (Suh et al, 2000(Suh et al, , 2006Hellmich et al, 2004Hellmich et al, , 2007, and activate poly(ADP-ribose) polymerases (PARP) (Laplaca et al, 1999;Besson et al, 2003;Satchell et al, 2003;Clark et al, 2007).…”

Lesão encefálica hipóxica em vítimas fatais de acidente de trânsito: prevalência, distribuição e associação com tempo de sobrevida e outras lesões cranioencefálicas e extracranianas

“…Embora haja evidências clínicas e experimentais de que, após o TCE, o cérebro torna-se particularmente susceptível à hipóxia 18,[22][23][24] , lesão neuronal de tipo isquêmico pode ser encontrada mesmo sem evidências de insultos hipóxico-isquêmicos 6,[25][26][27] . Em ambas as situações de TCE com e sem insultos hipó-xico-isquêmicos, o evento neuroquímico chave que parece desencadear a lesão neuronal é o aumento da concentração extracelular de glutamato, seguido do fluxo maciço e súbito de íons através da membrana celular, envolvendo o efluxo de potássio e o influxo de sódio, cálcio e outros íons, aumento da glicólise, acúmulo de ácido lático e liberação de áci-dos graxos livres (mecanismo excitotóxico) [27][28][29] .…”

“…Em ambas as situações de TCE com e sem insultos hipó-xico-isquêmicos, o evento neuroquímico chave que parece desencadear a lesão neuronal é o aumento da concentração extracelular de glutamato, seguido do fluxo maciço e súbito de íons através da membrana celular, envolvendo o efluxo de potássio e o influxo de sódio, cálcio e outros íons, aumento da glicólise, acúmulo de ácido lático e liberação de áci-dos graxos livres (mecanismo excitotóxico) [27][28][29] .…”

Substance-Related Disorders and Somatic Symptoms: How Should Clinicians Understand the Associations?

“…kainate, NMDA, or AMPA receptors-, supplemented by release of Ca 2+ from intracellular stores subsequent to mGluR activation, leading to intracellular Ca 2+ overload [50]. Excitotoxicity also involves an imbalance of transmembrane Na + , Cl -and K + gradients, cell swelling [51] and formation of calcium precipitates in most CNS areas [52][53][54]. The complexity of the mechanisms involved in glutamatergic neurotransmission makes it already apparent that a number of 10/48 abnormalities, pre-synaptic, post-synaptic or glial, alone or in combination can be excitotoxic.…”