Cardiopulmonary Arrest and Resuscitation Disrupts Cholinergic Anti-Inflammatory Processes: A Role for Cholinergic α7 Nicotinic Receptors

Abstract

Cardiac arrest is a leading cause of death worldwide. While survival rates following sudden cardiac arrest remain relatively low, recent advancements in patient care have begun to increase the proportion of individuals who survive cardiac arrest. However, many of these individuals subsequently develop physiological and psychiatric conditions that likely result from ongoing neuroinflammation and neuronal death. The present study was conducted to better understand the pathophysiological effects of cardiac arrest on neuronal cell death and inflammation, and their modulation by the cholinergic system. Using a well validated model of cardiac arrest, here we show that global cerebral ischemia increases microglial activation, proinflammatory cytokine mRNA expression (interleukin-1␤, interleukin-6, tumor necrosis factor-␣), and neuronal damage. Cardiac arrest also induces alterations in numerous cellular components of central cholinergic signaling, including a reduction in choline acetyltransferase enzymatic activity and the number of choline acetyltransferasepositive neurons, as well as, reduced acetylcholinesterase and vesicular acetylcholine transporter mRNA. However, treatment with a selective agonist of the ␣7 nicotinic acetylcholine receptor, the primary receptor mediating the cholinergic anti-inflammatory pathway, significantly decreases the neuroinflammation and neuronal damage resulting from cardiac arrest. These data suggest that global cerebral ischemia results in significant declines in central cholinergic signaling, which may in turn diminish the capacity of the cholinergic anti-inflammatory pathway to control inflammation. Furthermore, we provide evidence that pharmacological activation of ␣7 nicotinic acetylcholine receptors provide significant protection against ischemia-related cell death and inflammation within a clinically relevant time frame.

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

“…Antagonists of this receptor, such as the drug memantine, are suitable for the treatment of AD. There may be a potential role of the alpha 7 nicotinic acetylcholine receptor in reducing inflammatory neurotoxicity in AD [50]. Zinc deficiency is commonly noted in both AD and T2D [31], [51].…”

Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest

“…), rats were fixed in the supine position on a heated operating platform, so to maintain rectal temperature close to 37 1C; this procedure was adopted to avoid wrong interpretation of data due to a possible protective role of hypothermia (Lee et al, 2012;Norman et al, 2011). Rats were instrumented with indwelling polyethylene catheters in a common carotid artery, to record arterial blood pressure, and into an iliac vein for treatments and blood sampling.…”

“…In CA patients, brain and heart damage occurring during ischemia and reperfusion are due to free radical discharge, inflammatory and apoptotic responses (Chalkias and Xanthos, 2012;Lee et al, 2012;Meybohm et al, 2009;Norman et al, 2011). Besides further studies on therapeutic hypothermiamainly known as efficient treatment for neuroprotection during CA -novel approaches to protect the heart and brain are under investigation, including hydrogen sulfide donors, activators of cholinergic pathways, carvedilol, and argon (Brücken et al, 2014;Kida et al, 2012;Kurita et al, 2010;Lee et al, 2012;Norman et al, 2011;Parnia et al, 2014;Yu et al, 2013).…”

“…Besides further studies on therapeutic hypothermiamainly known as efficient treatment for neuroprotection during CA -novel approaches to protect the heart and brain are under investigation, including hydrogen sulfide donors, activators of cholinergic pathways, carvedilol, and argon (Brücken et al, 2014;Kida et al, 2012;Kurita et al, 2010;Lee et al, 2012;Norman et al, 2011;Parnia et al, 2014;Yu et al, 2013).…”

Original article A transcript coding for a partially duplicated form of α7 nicotinic acetylcholine receptor is absent from the CD4 + T-lymphocytes of patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)

“…They are predominantly located in cholinergic and non-cholinergic presynaptic terminals, such as GABA-ergic interneurons [12]. The α7 nAChRs are also found in nerve terminals located in peripheral tissues and are involved in neuropeptide release and protection against inflammatory processes [32]. Of particular interest is the function of nAChRs in peripheral blood lymphocytes (PBLs) [21].…”