VascularLamotrigine attenuates cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits
Introduction
Cerebral vasospasm after aneurysmal SAH is characterized by the prolonged and reversible contraction of the cerebral arteries [29], [51]. This vasospasm is one of the most important factors affecting patients' prognoses. Various substances have been studied in the development of vasospasm, although the pathogenesis and treatment remain unclear [10], [21], [59].
Currently, LTG is used clinically for the treatment of partial secondarily generalized seizures [31], [37]. Several reports have indicated that LTG also possess efficacy in the treatment of bipolar affective disorders [30], [35]. Lamotrigine exerts its therapeutic effects through several mechanisms involving inhibition of voltage-dependent sodium channels [12], [36], [38], antagonistic effects on high-voltage–activated calcium channels [41], [49], [52], [53], and enhancement of transient potassium outward current [24], [61]. The effects of LTG on ion channels have been studied on neurons. Lamotrigine has also been studied in neuroprotection after global brain ischemia based on its effect in the inhibition of presynaptic release of glutamate via blockade of voltage-gated sodium channels [7], [8], [9], [17], [56]. This compound's stabilizing effect on the cell membrane and its ability to block Ca2+ channels and inhibit glutamate release raise the possibility that it might have a vasodilatory effect on vascular smooth muscle and consequent neuroprotective effect after aneurysmal SAH. Unlike L-type Ca2+ channel blockers such as nimodipine and nicardipine, LTG has not been studied in an animal model of vasospasm. However, its neuroprotective effect in ischemia has been widely studied using in vivo and in vitro animal models [8], [17], [60].
The aim of this study was to investigate, through the use of the single-hemorrhage rabbit model [3], [37], the effects of LTG on cerebral vasospasm and subsequent neural ischemia.
Section snippets
Materials and methods
All protocols were approved by Ministry of Health Ankara Diskapi Research and Education Hospital Ethics Committee. The animals were initially anesthetized with ketamine-rompun (35/10 mg/kg) intramuscularly, and all animals breathed spontaneously throughout the procedures. Arterial blood samples (Po2 and Pco2) were taken from each animal from the catheterized ear arteries for blood gas analysis during the procedures, and only those animals with Po2 greater than 70 mm Hg and Pco2 less than 40 mm
Results
All 35 animals survived to complete the study. The animals were code-numbered and grouped in a random fashion. Clinical observation of the rabbits revealed drowsiness and hypoactivity in animals in the SAH group as assessed by blinded veterinarians. Rabbits in the control group and LTG-treated groups were as active after the treatment as they were before treatment.
Discussion
Cerebral vasospasm is an important cause of cerebral ischemia. It occurs 3 or 4 days after SAH, with a peak of severity occurring a week after SAH, which results in patients having ischemic neurologic deficits [29]. The goal of treatment is the prevention of vasospasm and delayed ischemic neurologic deficits. Cerebral vasospasm results from multiple factors [26], [50]. Hemoglobin is a likely causative agent in cerebrovascular spasm, although the mechanism behind its possible effects remains
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