Methamphetamine and Post-traumatic Epileptogenesis: Investigating the Neuroprotective Effect of Methamphetamine on Post-traumatic Seizures Caused by Traumatic Brain Injury

Author

Debbie Smith, The University of MontanaFollow

Year of Award

2015

Document Type

Dissertation - Campus Access Only

Degree Type

Doctor of Philosophy (PhD)

Degree Name

Neuroscience

Department or School/College

Department of Biomedical and Pharmaceutical Sciences

Committee Chair

David J. Poulsen

Commitee Members

Fernando Cardozo, Thomas Rau, Karen Wilcox, Josh Lawrence

Keywords

Epilepsy, Methamphetamine, Neuroinflammation, Neuroprotection, Seizures, Traumatic Brain Injury

Abstract

The research presented here investigated the efficacy of methamphetamine treatment as a neuroprotective agent against the development of post-traumatic seizures. We tested the ability of methamphetamine to modify electrographic events, post-traumatic seizures and susceptibility to pharmacologically induced seizures caused by traumatic brain injury. We also investigated several possible molecular mechanisms for the effect of methamphetamine on post-traumatic seizures. Specifically, we examined neuroinflammation, the loss of inhibitory interneurons, glutamate transport capacity and the loss of hilar mossy cells following severe traumatic brain injury and methamphetamine treatment. We discovered that treatment with methamphetamine shortly after severe traumatic brain injury causes a transient bilateral increase of Iba1 labeling within the granule cell layer of the dentate gyrus but does not alter the overall temporal-spatial progression of neuroinflammation in general throughout the brain. In addition, we showed that administering methamphetamine shortly after injury reduced abnormal electroencephalographic spiking patterns, incidence of spontaneous behavioral seizures and increased susceptibility to pharmacologically induced seizures caused by traumatic brain injury. Our results also showed that modulating the loss of somatostatin interneurons or mossy cells, or changes in glutamate transporter-1 expression did not have a major effect on post-traumatic epileptogenesis in our model. Overall, these research findings suggest a promising role for methamphetamine as a neuroprotective agent against post-traumatic seizures.

Recommended Citation

Smith, Debbie, "Methamphetamine and Post-traumatic Epileptogenesis: Investigating the Neuroprotective Effect of Methamphetamine on Post-traumatic Seizures Caused by Traumatic Brain Injury" (2015). Graduate Student Theses, Dissertations, & Professional Papers. 4595.
https://scholarworks.umt.edu/etd/4595