Activation of acetylcholinesterase after U-74389G administration in a porcine model of intracerebral hemorrhage

Abstract

Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes. Despite high incidence, morbidity and mortality, the precise pathophysiology of spontaneous ICH is not fully understood, while there is little data concerning the mechanisms that follow the primary insult of the hematoma formation. The cholinergic system, apart from its colossal importance as a neurotransmission system, seems to also play an important role in brain injury recovery. It has been recently suggested that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself. We, herein, report the findings of our study concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound enzyme involved in cholinergic neurotransmission) in a porcine model of spontaneous ICH, with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates the activation of AChE activity following U-74389G administration. The lazaroid U-74389G seems to be an established neuroprotectant and this is the first report of its supporting role in the enhancement of cholinergic response to the induction of ICH.

MicroRNA-21 Overexpression Promotes the Neuroprotective Efficacy of Mesenchymal Stem Cells for Treatment of Intracerebral Hemorrhage

“…Intracerebral hemorrhage is characterized by primary hematoma formation and secondary injury, which gives rise to neural cell death and neurological dysfunction ( 32 , 33 ). Apoptosis of neurons is one of the major features of the process of ICH.…”

Neuronal tumour necrosis factor-α and interleukin-1β expression in a porcine model of intracerebral haemorrhage: Modulation by U-74389G

“…The used model of experimental ICH is known to induce perihaematomal oxidative stress (Wagner, 2007;Wagner et al, 1996), and we have recently described the modulations of crucial adenosinetriphosphatases activities (Bimpis et al, 2013) and AChE activity (Bimpis et al, 2012). In the present study, we studied the modulations of TNF-α and IL-1β, at 4 and 24 h after the onset of ICH.…”

Relevance of Porcine Stroke Models to Bridge the Gap from Pre-Clinical Findings to Clinical Implementation

“…This model has also been replicated by other groups [ 174 , 175 , 179 , 180 , 181 , 182 ], as well as using the double injection method without the previous balloon catheter [ 168 , 170 ]. A similar method has been used by Bimpis et al; in their approach a balloon is inflated and, while decompressed, the autologous blood is injected [ 184 , 185 , 186 ]. In a recent study, injection of blood to the target region of the brain was performed after a craniotomy, but this was only performed to apply focused ultrasounds to liquefy induced intracerebral blood clots [ 165 ].…”