Crotalus Snake Venom Preconditioning to Prevent Surgical Brain Injury

<p>Preventive measures are increasingly relevant to medical practice. Preconditioning, a preemptive therapy that administers mildly harmful stimuli to induce endogenous protective mechanisms before major injury, has been shown to minimize injury in many animal models. Given the elective nature of most neurosurgical procedures, the surgical brain injury (SBI) rodent model provides an ideal platform for preconditioning. Our work shows that preconditioning with Crotalus rattlesnake venom, known for its hemorrhagic and inflammatory effects, mitigates some harmful effects of SBI. We have identified two proteins of interest in Crotalus venom: snake venom metalloproteinase (SVMP), an enzyme with hemorrhagic effects, and phospholipase A2 (PLA2), an enzyme upstream to cyclooxygenase-2 (COX-2) in the inflammatory cascade. We have found that preconditioning Crotalus venom increases endogenous fibrinogen, decreases perioperative hemorrhage, attenuates COX-2 activity, and reduces postoperative brain edema. Further understanding of these enzymes may yield a novel, preventive approach to reducing perioperative hemorrhage and edema in elective neurosurgical procedures.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Basic Sciences

Year

2015

Author dc:creator

• Kim, Cherine Hee-Sun

Contributors dc:contributor

• Zhang, John H.
• Duerksen-Hughes, Penelope
• Huang, Helen
• Obenaus, Andre
• Tang, Jiping

• Biochemistry
• Biochemistry, Biophysics, and Structural Biology
• Medical Biochemistry
• Medicine and Health Sciences
• Crotalid Venoms - Therapeutic Use; Crotalus - Metabolism; Brain Injuries - Surgery; Brain Edema - Drug Therapy; Postoperative Hemorrhage; Neuroprotective Agents; Phospholipases - Antagonist & Inhibitors; Matrix Mettaloproteinase Inhibitors
• Preconditioning; Endogenous Protective Mechanisms; Surgical Brain Injury Rodent Model; Endogenous Fibrinogen; Perioperative Hemorrhage; Postoperative Brain Edema

Statement dc:rights

• This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/224

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1237