Acetyl-L-carnitine and oxaloacetate in post-treatment against LTP impairment in a rat ischemia model. An in vitro electrophysiological study

Abstract

A high proportion of research relating to cerebral ischemia focuses on neuroprotection. The application of compounds normally present in the organism is popular, because they do not greatly influence the synaptic activity by receptor modulation, and can be administered without serious side effects. Oxaloacetate (OxAc) and acetyl-L-carnitine (ALC) are such favorable endogenous molecules. ALC can exert a protective effect by improving the energy state of the neurons under ischemic conditions. A promising neuroprotective strategy is glutamate scavenging, which can be achieved by the intravenous administration of OxAc. This study involved the possible protective effects of ALC and OxAc in different post-treatment protocols against long-term potentiation (LTP) impairment. Ischemia was induced in rats by 2-vessel occlusion, which led to a decreased LTP relative to the control group. High-dose (200 mg/kg) ALC or OxAc post-treatment resulted in a higher potentiation relative to the 2VO group, but it did not reach the control level, whereas low-dose ALC (100 mg/kg) in combination with OxAc completely restored the LTP function. Many previous studies have concluded that ALC can be protective only as pretreatment. The strategy described here reveals that ALC can also be neuroprotective when utilized as post-treatment against ischemia.

Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen–glucose deprivation

“…The preparation and maintenance of rat hippocampal slices were described previously (Kocsis et al, 2014;Kocsis et al, 2015). Briefly, the animals were decapitated and the middle parts of the hippocampi were placed in ice-cold artificial cerebrospinal fluid (aCSF) composed of (in mM): 130 NaCl, 3.5 KCl, 1 NaH 2 PO 4 , 24 NaHCO 3 , 1 CaCl 2 , 3 MgSO 4 and 10 D-glucose (all from Sigma, Germany), saturated with 95% O 2 + 5% CO 2 .…”

“…ALC is actively transported across the bloodbrain barrier to the brain (Burlina et al 1989), where it has a relative high concentration (Shug et al 1982). Several studies have demonstrated the neuroprotective effect of ALC against different neurodegenerative diseases, such as Alzheimer's disease, ischemia or neuropathic 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 4 investigated the neuroprotective effect of ALC against global hypoperfusion in a 2-vessel occlusion (2VO) model (Kocsis et al 2014, Kocsis et al 2015. The effects of ALC were also tested on striatal slices in an in vitro ischemia model, where it prevented the loss of the recorded field excitatory postynaptic potentials (fEPSPs) through the activation of M2 muscarinic receptors and the choline uptake system (Picconi et al 2006).…”

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

“…All these derivatives can transport therapeutic compounds through the BBB [161]. Over the past 5 years, the interest in the therapeutic potential of l-carnitine and acetyll-carnitine (ALCAR) for the transport of compounds across the BBB and for neuroprotection has significantly increased [162][163][164][165][166][167].…”