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The role of glutamate, calcium and magnesium in secondary brain injury


Correspondence: Dr Susan Leonard, Animal Emergency Hospital, 2 Cardinal Park Drive, Suite 101B, Leesburg, VA 20175, USA. Tel.: 703-777-5755; Fax: 703-777-9968; E-mail:


Objective: To review the roles that glutamate, calcium and magnesium play in both normal brain function and in the events following traumatic brain injury.

Human data synthesis: Elevated extracellular brain glutamate levels have been well documented in humans following traumatic brain injury. Therapies focusing on glutamate receptor antagonists have not yet been shown to have clinical effectiveness significant enough to outweigh the side effects. Newer strategies are currently being explored focusing on the many secondary cellular cascades interacting to culminate in cell injury and death.

Veterinary data synthesis: Derangements in glutamate, calcium and magnesium have been well documented in animals following traumatic brain injury. Research studies using animal models other than small laboratory animals such as rats, mice and rabbits are very limited. Prospective veterinary clinical trials in dogs and cats are needed to determine the potential success that various therapeutic strategies might have in the field of small animal emergency and critical care medicine.

Conclusions: Alterations in the levels of glutamate, calcium and magnesium play a critical role in secondary brain injury. The future development of clinically-tolerated and effective antagonists of glutamate, glutamate receptors, and other downstream mediators has the potential to revolutionize the therapy of traumatic brain injured patients.