Lipoic Acid Treatment after Brain Injury: Study of the Glial Reaction

After trauma brain injury, oxidative substances released to the medium provoke an enlargement of the initial lesion, increasing glial cell activation and, occasionally, an influx of immune cells into the central nervous system, developing the secondary damage. In response to these stimuli, microglia are activated to perform upregulation of intracellular enzymes and cell surface markers to propagate the immune response and phagocytosis of cellular debris. The phagocytosis of debris and dead cells is essential to limit the inflammatory reaction and potentially prevent extension of the damage to noninjured regions. Lipoic acid has been reported as a neuroprotectant by acting as an antioxidant and anti-inflammatory agent. Furthermore, angiogenic effect promoted by lipoic acid has been recently shown by our group as a crucial process for neural regeneration after brain injury. In this work, we focus our attention on the lipoic acid effect on astroglial and microglial response after brain injury. 1. Introduction Traumatic brain injury (TBI) is a complex process involving a broad spectrum of symptoms and long-term consequences including disabilities [1]. As a consequence of the primary insult, many molecules from injured and dead cells induce microglial and astroglial activation [2] and disruption of the blood-brain barrier (BBB) [3]. In addition to the direct loss of tissue caused by the trauma, secondary mechanisms leading to additional tissue injury are important for outcome and therefore constitute important therapeutic targets [4]. Recently, interest has been focused on oxidative stress as a mechanism involved in the development of secondary brain damage [5]. After brain injury, a local increase in glial cell activation occurs and, occasionally, an influx of immune cells goes into the central nervous system (CNS). Accumulation of blood born immune cells at the side of the lesion is paralleled by activation of CNS-resident astrocytes and microglia, where they latter transform into phagocytic macrophages [6]. The use of lipoic acid (LA) on stroke and TBI animal models seems to be effective, restoring the BBB disruption and normalizing the astrocytic/microglial activation and glutathione (GSH) levels [7–9]. LA is well known as a natural cofactor for mitochondrial enzymes and is critical in breaking down fatty acids, which further enhance cellular energy efficiency. Recent findings obtained by our group show that LA works as a good neuroprotectant by acting as an antioxidant, increasing the antioxidant capacity of the tissue, decreasing the astroglial