Cerebral ischemia and infarction

Basic pathophysiology of cerebral ischemia and infarcts was first studied using PET. In rather exten-... 

Moyamoya seems to be mainly confined to the Japanese and other Asians, and in most cases the cause is unknown (Bruno et al. 1988 Chiu et al. 1998). Some cases are familial (Kitahara et al. 1979) others appear to be caused by a generalized fibrous disorder of arteries (Aoyagi et al. 1996), and a few may result from a congenital hypoplastic anomaly affecting arteries at the base of the brain, or associated with Down s syndrome (Cramer et al. 1996). The syndrome may present in infancy with recurrent episodes of cerebral ischemia and infarction, mental retardation, headache, epileptic seizures and, occasionally, involuntary movements. In adults, subarachnoid or primary intracerebral hemorrhage are also common owing to rupture of collateral vessels. There have also been a few reports of associated intracranial aneurysms (Iwama et al. 1997) and also of cerebral arteriovenous malformations. 

Blumberg, R. M., Cady, E. B., Wigglesworth, J. S. etal. Relation between delayed impairment of cerebral metabolism and infarction following transient focal hypoxia-ischemia in the developing brain. Exp. Brain Res. 113 130-137, 1997. 

It is known from animal models with global ischemia and traumatic brain injury that moderate hypothermia attenuates secondary brain damage by reducing cerebral ischemia and postischemic brain edema and preserving the blood-brainbarrier. Even though hypothermia has potent cerebroprotective effects after experimental focal ischemia, clinical studies on hypothermic therapy after MCA infarction were not available until recently. We performed a pilot study investigating the efficacy, feasibility, and safety of induced moderate hypothermia in the therapy of patients with acute, severe MCA infarction and increased ICP. 

Finally, prostaglandins from COX-2 may play an important role in certain neurological disorders. For example, the prevalence of Alzheimer s disease seems to be lower in those patients that take NSAIDs [51]. COX-2 im-munoreactivity increases in certain brain tissues following cerebral ischemia and the upregulation of COX-2 has been implicated in delayed neuronal death. In rodent studies, selective COX-2 inhibitors attenuated the infarct volume in the hemisphere where the injury was induced. The mechanism by which selective inhibitors showed activity in this model was attributed to inhibition of prostaglandin E2 (PGE2) formation by COX-2 [52]. 

Despite the extensive effort of Feng et al. [310-331, 333-345], the mechanisms underlying the cerebro-protective actions of phthalides 30, 31 and 32 remain largely unclear. One of the possible reasons is that the authors often failed to demonstrate any causation or even correlation between the butylphthalide-mediated cerebro-protective responses and the various mechanisms proposed for example, direct evidence of protection such as reduction of infarct size was not reported in the mechanistic studies. The lack of consistency in the experimental protocols employed between the antiischemia and mechanism studies, such as 24-hour MCAO without reperfusion versus 2-hour MCAO with 24-hour reperfusion, also renders direct comparisons and correlations difficult (see Table 4). Moreover, some ambiguous data presentations and inadequate statistical analysis further complicated the interpretation of results in a number of studies. Nevertheless, these phthalides remain as potential therapeutic agents for the treatment of cerebral ischemia, and phthalide 30 was claimed to be effective for the treatment of cerebrovascular disease in a Chinese patent [7]. 

Veltkamp R, Warner DS, Domoki F, Brinkhous AD, Toole JF, Busija DW. Hyperbaric oxygen decreases infarct size and behavioral deficit after transient focal cerebral ischemia in rats. Brain Res 2000 853 68-73. 

Imaizumi, S., Woolworth, V., Fishman, R.A. and Chan, P.H. (1990). Liposome-entrapped superoxide dismutase reduces infarction in cerebral ischemia in rats. Stroke 21, 1312-1317. 

Koketsu, N., Berlove, D. J., Moskowitz, M. A., Kowall, N. W., Caday, C. G. and Finklestein, S. P. Pretreatment with intraventricular basic fibroblast growth factor decreases infarct size following focal cerebral ischemia in rats. Ann. Neurol. 35 451-457,1994. 

The final result of both thrombus formation and embolism is arterial occlusion, decreasing cerebral blood flow and causing ischemia and ultimately infarction distal to the occlusion. 

Jin, K., Sun, Y., Xie, L., Childs, J., , X.O., Greenberg, D.A. (2004). Post-ischemic administration of heparin-binding epidermal growth factor-like growth factor (HB-EGF) reduces infarct size and modifies neurogenesis after focal cerebral ischemia in the rat. J... 

An early in vivo study in the model of global forebrain ischemia in the gerbil showed that a selective agonist of A3AR, IB-MECA, acutely administered 15 min prior to ischemia, impaired post-ischemic blood flow, increased mortality and exacerbated the loss of hippocampal neurons (von Lubitz et al. 1994). IB-MECA administration 20 min prior to transient middle cerebral ischemia also resulted in a significant increase in infarct size(von Lubitz et al. 2001). 

Cerebral infarction has also been reported in association with the use of desmopressin in children (31,32). One of these cases involved a 7-month-old child with congenital nephrotic syndrome who developed a cerebral infarction after surgery (31). One child developed cerebral ischemia after Varicella infection and desmopressin for enuresis (32). 

Rauca, C., Henrich-Noack, P., Schafer, K., Hollt, V., and Reymann, K. G. (1998). (5)-4C3HPG reduces infarct size after focal cerebral ischemia. Neuropharmacology 37, 1649—1652. 

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