Baicalein has been shown to offer neuroprotection in the ischemic brain, but its effect in subarachnoid hemorrhage (SAH) is unknown. The authors used a double-hemorrhage model to study the role of early baicalein treatment in SAH.
Subarachnoid hemorrhage was induced in male Wistar rats through a repeat injection of autologous blood at a 48-hour interval. Rats subjected or not subjected to SAH received a 30-mg/kg baicalein injection 3 hours after SAH and daily for 6 consecutive days, and results were compared with those obtained in vehicle-treated control rats. Mortality of the rats was recorded. Neurological outcome was assessed daily. Cerebrospinal fluid dialysates were collected and examined for glutamate concentrations. Cerebral vasospasm (CVS), brain water content, neuron variability, expression of glutamate transporter–1 (GLT-1), immunoreactivity of astrocyte, and level of malondialdehyde, activities of superoxide dismutase (SOD), and catalase in brain tissues content were determined on post-SAH Day 7.
Mortality rate, neuronal degeneration, brain water content, and CVS were decreased and neurological function improved in the baicalein-treated rats. Baicalein increased astrocyte activity and preserved GLT-1, which attenuated the glutamate surge after SAH. Baicalein also provided antioxidative stress by preserving activities of SOD and catalase and decreased malondialdehydelevel after SAH. The glutamate, body weight, neurological scores, and glial fibrillary acidic protein activity were significantly correlated. The CVS was correlated with neuronal degeneration, and GLT-1 was correlated with oxidative stress.
Early baicalein treatment attenuated CVS and limited neurological injury following SAH. These data may indicate clinical utility for baicalein as an adjunct therapy to reduce brain injury and improve patient outcomes.
Please include this information when citing this paper: published online May 31, 2013; DOI: 10.3171/2013.4.JNS121919.
Anderson CM, & Swanson RA: Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32:1–14, 2000
Cahill J, , Calvert JW, & Zhang JH: Mechanisms of early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab 26:1341–1353, 2006. (Erratum in J Cereb Blood Flow Metab 26:1463, 2006)
Chen SF, , Hsu CW, , Huang WH, & Wang JY: Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury. Br J Pharmacol 155:1279–1296, 2008
Claassen J, , Carhuapoma JR, , Kreiter KT, , Du EY, , Connolly ES, & Mayer SA: Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome. Stroke 33:1225–1232, 2002
Dávalos A, , Castillo J, , Serena J, & Noya M: Duration of glutamate release after acute ischemic stroke. Stroke 28:708–710, 1997
Dumont AS, , Dumont RJ, , Chow MM, , Lin CL, , Calisaneller T, & Ley KF, et al.: Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 53:123–135, 2003
Fagan SC, , Hess DC, , Hohnadel EJ, , Pollock DM, & Ergul A: Targets for vascular protection after acute ischemic stroke. Stroke 35:2220–2225, 2004
Garcia JH, , Wagner S, , Liu KF, & Hu XJ: Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke 26:627–635, 1995
Germanò A, , Caffo M, , Angileri FF, , Arcadi F, , Newcomb-Fernandez J, & Caruso G, et al.: NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat. J Neurotrauma 24:732–744, 2007
Gules I, , Satoh M, , Clower BR, , Nanda A, & Zhang JH: Comparison of three rat models of cerebral vasospasm. Am J Physiol Heart Circ Physiol 283:H2551–H2559, 2002
Huang WH, , Lee AR, & Yang CH: Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI. Biosci Biotechnol Biochem 70:2371–2380, 2006
Jeon H, , Ai J, , Sabri M, , Tariq A, , Shang X, & Chen G, et al.: Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage. BMC Neurosci 10:103, 2009
Jin G, , Arai K, , Murata Y, , Wang S, , Stins MF, & Lo EH, et al.: Protecting against cerebrovascular injury: contributions of 12/15-lipoxygenase to edema formation after transient focal ischemia. Stroke 39:2538–2543, 2008
Kerman M, , Kanter M, , Coşkun KK, , Erboga M, & Gurel A: Neuroprotective effects of caffeic acid phenethyl ester on experimental traumatic brain injury in rats. J Mol Histol 43:49–57, 2012
Kubo M, , Matsuda H, , Tanaka M, , Kimura Y, , Okuda H, & Higashino M, et al.: Studies on Scutellariae radix. VII Anti-arthritic and anti-inflammatory actions of methanolic extract and flavonoid components from Scutellariae radix Chem Pharm Bull (Tokyo) 32:2724–2729, 1984
Kuo CP, , Lu CH, , Wen LL, , Cherng CH, , Wong CS, & Borel CO, et al.: Neuroprotective effect of curcumin in an experimental rat model of subarachnoid hemorrhage. Anesthesiology 115:1229–1238, 2011
Lee HH, , Yang LL, , Wang CC, , Hu SY, , Chang SF, & Lee YH: Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate-and glucose deprivation-induced neuronal death. Brain Res 986:103–113, 2003
Lo EH, , Moskowitz MA, & Jacobs TP: Exciting, radical, suicidal: how brain cells die after stroke. Stroke 36:189–192, 2005
López-Redondo F, , Nakajima K, , Honda S, & Kohsaka S: Glutamate transporter GLT-1 is highly expressed in activated microglia following facial nerve axotomy. Brain Res Mol Brain Res 76:429–435, 2000
O'Callaghan JP, & Sriram K: Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity. Expert Opin Drug Saf 4:433–442, 2005
Ostrowski RP, , Colohan AR, & Zhang JH: Molecular mechanisms of early brain injury after subarachnoid hemorrhage. Neurol Res 28:399–414, 2006
Prunell GF, , Svendgaard NA, , Alkass K, & Mathiesen T: Delayed cell death related to acute cerebral blood flow changes following subarachnoid hemorrhage in the rat brain. J Neurosurg 102:1046–1054, 2005
Rossi DJ, , Brady JD, & Mohr C: Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci 10:1377–1386, 2007
Rothoerl RD, , Schebesch KM, , Kubitza M, , Woertgen C, , Brawanski A, & Pina AL: ICAM-1 and VCAM-1 expression following aneurysmal subarachnoid hemorrhage and their possible role in the pathophysiology of subsequent ischemic deficits. Cerebrovasc Dis 22:143–149, 2006
Sabri M, , Kawashima A, , Ai J, & Macdonald RL: Neuronal and astrocytic apoptosis after subarachnoid hemorrhage: a possible cause for poor prognosis. Brain Res 1238:163–171, 2008
Seçkin H, , Yigitkanli K, , Besalti O, , Kosemehmetoglu K, , Ozturk E, & Simsek S, et al.: Lamotrigine attenuates cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. Surg Neurol 70:344–351, 2008
Sehba FA, , Pluta RM, & Zhang JH: Metamorphosis of subarachnoid hemorrhage research: from delayed vasospasm to early brain injury. Mol Neurobiol 43:27–40, 2011
Stegmayr B, , Eriksson M, & Asplund K: Declining mortality from subarachnoid hemorrhage: changes in incidence and case fatality from 1985 through 2000. Stroke 35:2059–2063, 2004
Suarez JI, , Tarr RW, & Selman WR: Aneurysmal subarachnoid hemorrhage. N Engl J Med 354:387–396, 2006
Sullivan SM, , Björkman ST, , Miller SM, , Colditz PB, & Pow DV: Morphological changes in white matter astrocytes in response to hypoxia/ischemia in the neonatal pig. Brain Res 1319:164–174, 2010
Sung CS, , Wen ZH, , Chang WK, , Ho ST, , Tsai SK, & Chang YC, et al.: Intrathecal interleukin-1beta administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord. Brain Res 1015:145–153, 2004
van Landeghem FK, , Weiss T, , Oehmichen M, & von Deimling A: Decreased expression of glutamate transporters in astrocytes after human traumatic brain injury. J Neurotrauma 23:1518–1528, 2006
Vicente E, , Degerone D, , Bohn L, , Scornavaca F, , Pimentel A, & Leite MC, et al.: Astroglial and cognitive effects of chronic cerebral hypoperfusion in the rat. Brain Res 1251:204–212, 2009
Wu CT, , Wen LL, , Wong CS, , Tsai SY, , Chan SM, & Yeh CC, et al.: Temporal changes in glutamate, glutamate transporters, basilar arteries wall thickness, and neuronal variability in an experimental rat model of subarachnoid hemorrhage. Anesth Analg 112:666–673, 2011
Xi G, , Hua Y, , Keep RF, , Younger JG, & Hoff JT: Brain edema after intracerebral hemorrhage: the effects of systemic complement depletion. Acta Neurochir Suppl 81:253–256, 2002
All Time | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1364 | 301 | 15 |
Full Text Views | 214 | 11 | 1 |
PDF Downloads | 159 | 14 | 1 |
EPUB Downloads | 0 | 0 | 0 |