Transient Elevation of Interstitial N‐Acetylaspartate in Reversible Global Brain Ischemia

Abstract

We evaluated the changes of interstitial N‐acetylaspartate (NAA) concentration ([NAA]e) in rat striatum by microdialysis following transient global ischemia and depolarization. The dialysate NAA concentration ([NAA]d) values were corrected for the in vivo recovery to obtain [NAA]e, by the use of [3H]mannitol in the perfusion fluid. During global ischemia the relative loss (RL) of [3H]mannitol decreased to 40% of preischemic values, reflecting the decrease in extracellular volume fraction. During reperfusion RL of [3H]mannitol quickly normalized. The [NAA]d doubled during transient ischemia, which, after correction for in vivo recovery, corresponds to a fivefold increase in [NAA]e (p < 0.05). Reperfusion induced a >10‐fold increase of [NAA]e (p < 0.01) with subsequent normalization after 45 min. KCI at 100 mM caused a reversible 50% reduction in RL of [3H]mannitol and a three times increase in [NAA]e (p < 0.05) but no further increase when normal perfusate was reintroduced. The mechanisms of NAA release from neurons are unknown but may involve the activation of unknown channels/carriers—possibly in relation to a volume regulatory response. The present study shows that the distribution of NAA in brain is dynamically regulated in acute ischemia and suggests that changes of NAA levels could be caused by other means than neuronal loss.

Evidence that N-acetyaspartylglutamate is the astrocyte-targeted neurovascular coupling agent that regulates slow tonic control of brain blood flow

“…This has been observed for NAA in rat microdialysis studies where neurons were depolarized by K + [25,26] and for NAA and NAAG in a rat brain slice superfusion study where depolarization was by electrical stimulation at 15 Hz, 20mA for 3 min and NAA and NAAG were observed to be released at the same relative % rate [27]. The release of NAA and NAAG is likely primarily non-synaptic since neurons do not express ASPA or NAAG peptidase that would be and increasing the supply of oxygen and glucose.…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…NAA can be released to the interstitial space upon osmotic challenges (e.g. Sager et al, 1997;Bothwell et al, 2001) suggesting that it may also play a role in osmorelulation.…”

Inheritance in OCD in Moslems

“…After its release from neurons, NAA is taken up and hydrolyzed by oligodendrocytes to act as a source of acetyl groups in a variety of metabolic processes, including myelin synthesis, lipid repair/fatty acid synthesis, osmotic regulation, and anti-inflammatory action. Reduced dAC NAA levels may, thus, reflect a variety of underlying metabolic and biochemical changes that, when considered in the context of the present findings, suggest that OCD patients have fewer healthy neurons in the region, necessitating the recruitment of adjacent and other task-related brain regions (e.g., the SMA, the lateral premotor, and the superior parietal) to perform at levels comparable with controls [12][13][14][15][16][17].…”