Alpha-II spectrin breakdown products in aneurysmal subarachnoid hemorrhage: a novel biomarker of proteolytic injury.
OBJECTIVE
Aneurysmal subarachnoid hemorrhage (ASAH) is a serious event with grave consequences. Delayed ischemic neurological deficits caused by cerebral arterial vasospasm contribute significantly to death and disability. Biomarkers may reflect brain injury and provide an early warning of impending neurological decline and stroke from ASAH-induced vasospasm. Alpha-II spectrin is a cytoskeletal protein whose breakdown products are candidate surrogate markers of injury magnitude, treatment efficacy, and outcome. In addition, all spectrin breakdown products (SBDPs) can provide information on the proteolytic mechanisms of injury.


METHODS
Twenty patients who received a diagnosis of Fisher Grade 3 ASAH were enrolled in this study to examine the clinical utility of SBDPs in the detection of cerebral vasospasm in patients with ASAH. All patients underwent placement of a ventriculostomy for continual cerebrospinal fluid drainage within 72 hours of ASAH onset. Cerebrospinal fluid samples were collected every 6 hours and analyzed using Western Blotting for SBDPs. Onset of vasospasm was defined as an acute onset of a focal neurological deficit or a change in Glasgow Coma Scale score of two or more points. All suspected cases of vasospasm were confirmed on imaging studies.


RESULTS
Both calpain- and caspase-mediated SBDP levels are significantly increased in patients suffering ASAH. The concentration of SBDPs was found to increase significantly over baseline level up to 12 hours before the onset of cerebral arterial vasospasm.


CONCLUSIONS
Differential expression of SBDPs suggests oncotic necrotic proteolysis may be predominant in acute brain injury after ASAH and cerebral arterial vasospasm.
Lewis
Stephen B
SB
Department of Neurological Surgery, University of Florida, Gainesville 32610, USA. lewis@neurosurgery.ufl.edu
Velat
Gregory J
GJ
Miralia
Lynn
L
Papa
Linda
L
Aikman
Jada M
JM
Wolper
Regina A
RA
Firment
Chris S
CS
Liu
Ming Chen
MC
Pineda
Jose A
JA
Wang
Kevin K W
KK
Hayes
Ronald L
RL
D000328:Adult; D000368:Aged; D015901:Angiography, Digital Subtraction; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002533:Cerebral Angiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D013049:Spectrin / Q000134:cerebrospinal fluid* / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000473:pathology*; D014057:Tomography, X-Ray Computed; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000473:pathology
D015415:Biomarkers; D013049:Spectrin; D002154:Calpain; D020169:Caspases