Research Update in
Neuroscience for Neurosurgeons

J. Marc Simard, M.D.,Ph.D.
Professor, Department of Neurosurgery
University of Maryland
Baltimore

"The SUR1-regulated NC(Ca-ATP) channel - a new player in CNS ischemia"

Outline

1. Basic properties of the NC(Ca-ATP) channel
   1. electrophysiology
   2. pharmacology
   3. pH

2. Cellular consequences of channel opening
   1. depolarization
   2. cytotoxic edema
   3. oncotic (necrotic) cell death

3. Channel up-regulation in CNS injury
   1. cerebral ischemia
   2. cerebral trauma
   3. spinal cord injury
   4. subarachnoid hemorrhage

4. Channel block
   1. Cerebral ischemia
   2. Spinal cord injury
   3. subarachnoid hemorrhage

Suggested reading: 1-9

1. Newly expressed SUR1-regulated NCCa-ATP channel mediates cerebral edema after ischemic stroke Nature Medicine 2006; 12:4-April
   
   
2. Endothelial sulfonylurea receptor 1– regulated NCCa-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury The Journal of Clinical Investigation Volume 117 Number 8 August 2007
   
   
3. Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage Journal of Cerebral Blood Flow & Metabolism (2008), 1–14 & 2008 ISCBFM
   
   
4. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications The Lancet 2007: Vol 6 March
   
   
5. Ayata C, Ropper AH. Ischaemic brain oedema. J Clin Neurosci 2002;9:113-24.
   
   
6. Simard JM, Kent TA, Chen M, Tarasov KV, Gerzanich V.
   Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications (PDF 307KB). Lancet Neurol 2007;6:258-68.
   
   
7. Simard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchenko L, Tsymbalyuk N, West GA, Gerzanich V.
   Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke (PDF 645KB). Nat Med 2006;12:433-40.
   
   
8. Kunte H, Schmidt S, Eliasziw M, Del Zoppo GJ, Simard JM, Masuhr F, Weih M, Dirnagl U. Sulfonylureas Improve Outcome in Patients With Type 2 Diabetes and Acute Ischemic Stroke (PDF 137KB). Stroke 2007.
   
   
9. Simard JM, Tsymbalyuk O, Ivanov A, Ivanova S, Bhatta S, Geng Z, Woo SK, Gerzanich V. Endothelial sulfonylurea receptor 1-regulated NC(Ca-ATP) channels mediate progressive hemorrhagic necrosis following spinal cord injury (PDF 1.06MB). J Clin Invest 2007;117:2105-13.

Copyright © 2008 The Society of Neurological Surgeons