Summary
The present study examined differences in intracerebral hemorrhage (ICH)-induced brain injury in male and female rats, whether delayed administration of 17β-estradiol can reduce ICH-induced brain damage, and whether these effects are estrogen receptor (ER)-dependent.
Male and female Sprague-Dawley rats received an infusion of 100-µL autologous whole blood into the right basal ganglia. The effects of 17β-estradiol (5 mg/kg, i.p.) on ICH-induced brain injury were examined by measuring brain edema and neurological deficits 24 hours later. Heme oxygenase-1 (HO-1) was investigated by immuno-analysis. Brain edema was significantly less in female compared to male rats. The ER antagonist ICI182,780 exacerbated ICHinduced brain edema in female but not in male rats, suggesting that ER activation during ICH is protective in female rats. Administration of 17β-estradiol to male (but not female) rats significantly reduced brain edema, neurological deficits, and ICH-induced increases in brain HO-1 levels when given 2 hours after ICH. This study showed that female rats have less ICH-induced injury than male rats. ER is involved in limiting ICH-induced injury in female rats. ICH-injury in male rats can be reduced by 17β-estradiol. Since 17β-estradiol treatment was effective in male rats, it could be a potential therapeutic agent for ICH.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Behl C, Skutella T, Lezoualch F, Post A, Widmann M, Newton CJ, Holsboer F (1997) Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Mol Pharmacol 51: 535–541
Culmsee C, Vedder H, Ravati A, Junker V, Otto D, Ahlemeyer B, Krieg JC, Krieglstein J (1999) Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: evidence for a receptor-independent antioxidative mechanism. J Cereb Blood Flow Metab 19: 1263–1269
Harder DR, Coulson PB (1975) Estrogen receptors and effects of estrogen on membrane properties of coronary vascular smooth muscle. J Cell Physiol 100: 375–382
Hurn PD, Brass LM (2003) Estrogen and stroke: a balanced analysis. Stroke 34: 338–341
Hurn PD, Littleton-Kearney MT, Kirsch JR, Dharmarajan AM, Traystman RJ (1995) Postischemic cerebral blood flow recovery in the female: effect of 17 beta-estradiol. J Cereb Blood Flow Metab 15: 666–672
Kase CS, Caplan LR (1994) Intracerebral Hemorrhage. Butterworth-Heinemann, Boston
Nakamura T, Keep RF, Hua Y, Schallert T, Hoff JT, Xi G (2004) Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. J Neurosurg 100: 672–678
Nakamura T, Xi G, Hua Y, Schallert T, Hoff JT, Keep RF (2004) Intracerebral hemorrhage in mice: model characterization and application for genetically modified mice. J Cereb Blood Flow Metab 24: 487–494
Roof RL, Hall ED (2000) Gender differences in acute CNS trauma and stroke: Neuroprotective effects of estrogen and progesterone. J Neurotrauma 17: 367–388
Sawada M, Alkayed NJ, Goto S, Crain BJ, Traystman RJ, Shaivitz A, Nelson RJ, Hurn PD (2000) Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse. J Cereb Blood Flow Metab 20: 112–118
Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST (2000) CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology 39: 777–787
Sheng Z, Kawano J, Yanai A, Fujinaga R, Tanaka M, Watanabe Y, Shinoda K (2004) Expression of estrogen receptors (alpha, beta) and androgen receptor in serotonin neurons of the rat and mouse dorsal raphe nuclei; sex and species differences. Neurosci Res 49: 185–196
Wagner KR, Hua Y, de Courten-Myers GM, Broderick JP, Nishimura RN, Lu SY, Dwyer BE (2000) Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol (Noisy-le-grand) 46: 597–608
Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G (2003) Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 34: 2964–2969
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer-Verlag
About this paper
Cite this paper
Nakamura, T. et al. (2006). Effects of endogenous and exogenous estrogen on intracerebral hemorrhage-induced brain damage in rats. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_47
Download citation
DOI: https://doi.org/10.1007/3-211-30714-1_47
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-30712-0
Online ISBN: 978-3-211-30714-4
eBook Packages: MedicineMedicine (R0)