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Postconcussive Syndrome Following Sports-Related Concussion

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Postconcussive Syndrome Following Sports-Related Concussion

Neurochemistry and Pathophysiology of PCS


The presence of PCS symptoms is believed to reflect brain injury with consequent pathophysiologic changes. The core components of these changes include diffuse axonal injury (DAI), abrupt neuronal depolarization, release of excitatory neurotransmitters, ionic shifts, changes in glucose metabolism, and altered cerebral blood flow (CBF). DAI occurs as a result of shear-strain forces on the brain and has been associated with significant morbidity postbrain injury. It remains difficult to identify DAI on traditional imaging or in laboratory analysis, however. Immediately postinjury, neurons attempt to restore homeostasis through a variety of mechanisms that use increasing amounts of adenosine triphosphate, triggering an increase in glucose metabolism and producing an initial hypermetabolic state. This is followed by a state of metabolic depression driven by ionic shifts, lactic acid generation, altered neurotransmission, inflammatory responses, decreased intracellular magnesium, free radical production, and decreased CBF. Physiologically, CBF is tightly coupled to neuronal activity and cerebral glucose metabolism; however, postinjury CBF may be reduced by 50% of normal, producing an energy crisis because of a mismatch of supply and demand in the setting of increased glucose use. The described process may explain why patients who are asymptomatic at rest can become symptomatic during physical or cognitive exertion. Other more systemic effects of concussion include heart rate variability, circadian rhythm disturbance, and altered cytochrome P450 systems. This widespread pathophysiology may have implications for treatment of PCS through pharmacological and nonpharmacologic means.

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