The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS

Abstract

Normal brain function is highly dependent on oxygen and nutrient supply and when the demand for oxygen exceeds its supply, hypoxia is induced. Acute episodes of hypoxia may cause a depression in synaptic activity in many brain regions, whilst prolonged exposure to hypoxia leads to neuronal cell loss and death. Acute inadequate oxygen supply may cause anaerobic metabolism and increased respiration in an attempt to increase oxygen intake whilst chronic hypoxia may give rise to angiogenesis and erythropoiesis in order to promote oxygen delivery to peripheral tissues. The effects of hypoxia on neuronal tissue are exacerbated by the release of many inflammatory agents from glia and neuronal cells. Cytokines, such as TNF-α, and IL-1β are known to be released during the early stages of hypoxia, causing either local or systemic inflammation, which can result in cell death. Another growing body of evidence suggests that inflammation can result in neuroprotection, such as preconditioning to cerebral ischemia, causing ischemic tolerance. In the following review we discuss the effects of acute and chronic hypoxia and the release of pro-inflammatory cytokines on synaptic transmission and plasticity in the central nervous system. Specifically we discuss the effects of the pro-inflammatory agent TNF-α during a hypoxic event.

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“…; Mukandala et al . ). This response is adaptive at a local level, as it reduces metabolic demands, enhancing the capacity of brain tissue to survive periods of limited O 2 supply, but hypoxic depression of respiratory network activity is maladaptive; i.e.…”

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“…It has been reported that under hypoxic insult, the activity of HIF-1 and expression of its associated downstream genes, such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO) are altered in a range of neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS) [4]. It has also been reported that hypoxia causes reduced synaptic transmission associated with neuronal death by causing neuronal dysfunction [5]. Thus, elucidation of pathophysiological mechanisms caused due to hypoxic insults on the cerebral nervous system (CNS); their therapeutic regulation awaits much importance.…”