engleski

Traumatic brain injury: therapeutic challenges

Traumatic brain injury (TBI) affects millions of people worldwide and represents the leading cause of mortality and disability, especially in the population bellow 45 years of age. TBI is not a single pathophysiological event and it includes primary and secondary injury patterns. The primary injury induces irreversible tissue damage that cannot be pharmacologically affected. Secondary brain injury, that is initiated at the moment of the impact, represents the complex cascade of different molecular, biochemical and metabolic processes including excitotoxicity and altered calcium homeostasis, mitochondrial damage and dysfunction, ischemia, oxidative stress, inflammation leading to a breakdown of the blood- brain barrier and the development of cerebral edema with subsequent tissue damage and cell death. These events have the central role in modern TBI management whose main goal is to improve patients’ outcomes. Today's pharmacotherapy of TBI is only supportive and it does not include an effective neuroprotective agent. The majority of research in the field of the TBI therapy has been focused primarily on drugs that target only particular steps in the cascade of pathophysiological events but because of multifactorial nature of the secondary injury, it is unlikely that it will result in a significant improvement of outcomes. Therefore, the recent pharmacological investigations are directed mainly toward multifunctional drugs that could affect different harmful pathomechanisms included in TBI. Here, our studies on the effects of two multifunctional compounds, an anticoagulant, enoxaparin, and a peroxisome proliferator-activated receptor γ agonist, pioglitazone, on the parameters of the rat brain damage suggesting their promising neuroprotective activity in experimental TBI, will be presented.

traumatic brain injury; therapy; neuroprotection

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