An enhanced understanding of the mechanisms that underlie the genesis of cerebral edema and raised ICP is critical for the development of more targeted and effective treatments.Īlthough factors associated with the pathogenesis of cerebral edema are not completely understood, neurogenic inflammation has been identified as a potential therapeutic target ( Stumm et al., 2001 Turner et al., 2006 Corrigan et al., 2016a). It is clear that current pharmacological and surgical interventions are inadequate as they target the symptoms, rather than the underlying cause of cerebral edema and concomitant rise in ICP ( Bardutzky and Schwab, 2007 Simard et al., 2007). However, although this procedure reduces compression on cerebral structures and the risk of life-threatening tonsillar herniation, it is also associated with increased morbidity in those aged greater than 60 years, the patient population in which stroke is most prevalent ( Jüttler et al., 2007 Das et al., 2019). This procedure rapidly alleviates pressure by removing a large portion of the skull and opening the dura overlying the brain, thereby providing space for the edematous brain to swell freely until cerebral edema resolves, typically beyond the first week following stroke ( Xiao-feng et al., 2005). In selected patients with malignant middle cerebral artery (MCA) territory infarction, surgical intervention with decompressive craniectomy (DC) may be required. Furthermore, the efficacy of other pharmacotherapies including corticosteroids and barbiturates remains ambiguous for the treatment of post-stroke cerebral edema ( Brogan and Manno, 2015). Pharmacological interventions for ICP management are limited, and while osmotic therapies (including mannitol and hypertonic saline) are used in some centers ( Zhang et al., 2018), there is no evidence that these therapies are independently effective in improving outcome. Despite the devastating impact of elevated ICP on patient outcome, clinical management remains sub-optimal. On MRI, midline shift and cerebral edema were more marked in vehicles compared to NK1-r treatment groups.Ĭonclusion: Two or three boluses of NK1-r antagonist treatment reduced ICP comparable to DC surgery, suggesting it may provide a novel alternative to invasive surgery for the management of elevated ICP.Įlevated intracranial pressure (ICP) arising as a result of malignant cerebral edema is the leading cause of death in the first week following stroke ( Hacke et al., 1996). 1×NK1 was ineffective in sustainably lowering ICP. Results: 2×NK1, 3×NK1 administration or DC surgery significantly ( p < 0.05) reduced ICP compared to vehicle. At 24 h post-stroke anesthetized animals underwent MRI followed by perfusion and brains removed and processed for histological assessment. ICP, blood pressure and blood gasses were monitored for 24 h post-stroke. Stroke animals were randomized into one of 5 treatments: 1×NK1 bolus (4 h), 2×NK1 bolus (4 h 9 h), 3×NK1 bolus (4 h 9 h 14 h), DC surgery (performed at 4 h) or saline vehicle. Methods: Anesthetized female Merino sheep (65 ± 6 kg, 18–24 months) underwent sham surgery ( n = 4) or permanent middle cerebral artery occlusion ( n = 22). Consequently, the current study compared the efficacy of NK1-r antagonist treatment to DC surgery in reducing ICP post-stroke in a clinically relevant ovine model. ![]() However, treatment has not been investigated in a large animal model, an important step toward clinical translation. NK1-r antagonist treatment ameliorates BBB dysfunction and cerebral edema in rodent stroke models. Neurogenic inflammation, mediated by substance P (SP) binding to the tachykinin NK1 receptor (NK1-r), is associated with blood-brain barrier (BBB) disruption, cerebral edema and poor outcome post-stroke. Accordingly, there is an urgent need for therapies that directly target the mechanisms of edema genesis. Existing pharmacotherapies do not target the underlying pathophysiology and are often ineffective in sustainably lowering ICP, whilst decompressive craniectomy (DC) surgery is life-saving yet with surgical/peri-operative risk and increased morbidity in the elderly. Background and Purpose: The morbidity and early mortality associated with stroke is largely attributable to cerebral edema and elevated intracranial pressure (ICP).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |