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Lithium upregulates growth-associated protein-43 (GAP-43) and postsynaptic density-95 (PSD-95) in cultured neurons exposed to oxygen-glucose deprivation and improves electrophysiological outcomes in rats subjected to transient focal cerebral ischemia following a long-term recovery period
- Source :
- Neurological Research. 44:870-878
- Publication Year :
- 2022
- Publisher :
- Informa UK Limited, 2022.
-
Abstract
- Lithium has numerous neuroplastic and neuroprotective effects in patients with stroke. Here, we evaluated whether delayed and short-term lithium treatment reduces brain infarction volume and improves electrophysiological and neurobehavioral outcomes following long-term recovery after cerebral ischemia and the possible contributions of lithium-mediated mechanisms of neuroplasticity.Male Sprague Dawley rats were subjected to right middle cerebral artery occlusion for 90 min, followed by 28 days of recovery. Lithium chloride (1 mEq/kg) or vehicle was administered via intraperitoneal infusion once per day at 24 h after reperfusion onset. Neurobehavioral outcomes and somatosensory evoked potentials (SSEPs) were examined before and 28 days after ischemia-reperfusion. Brain infarction was assessed using Nissl staining. Primary cortical neuron cultures were exposed to oxygen-glucose deprivation (OGD) and treated with 2 or 20 μM lithium for 24 or 48 h; subsequent brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density-95 (PSD-95), and synaptosomal-associated protein-25 (SNAP-25) levels were analyzed using western blotting.Compared to controls, lithium significantly reduced infarction volume in the ischemic brain and improved electrophysiological and neurobehavioral outcomes at 28 days post-insult. In cultured cortical neurons, BDNF, GAP-43, and PSD-95 expression were enhanced by 24- and 48-h treatment with lithium after OGD.Lithium upregulates BDNF, GAP-43, and PSD-95, which partly accounts for its improvement of neuroplasticity and provision of long-term neuroprotection in the ischemic brain.
- Subjects :
- Male
Neurons
Glycogen Synthase Kinase 3 beta
N-Methylaspartate
Brain-Derived Neurotrophic Factor
Sodium Dodecyl Sulfate
Infarction, Middle Cerebral Artery
General Medicine
Lithium
Receptors, N-Methyl-D-Aspartate
Brain Ischemia
Rats
Oxygen
Rats, Sprague-Dawley
GAP-43 Protein
Glucose
Neuroprotective Agents
Neurology
Animals
Neurology (clinical)
Lithium Chloride
Disks Large Homolog 4 Protein
Edetic Acid
Subjects
Details
- ISSN :
- 17431328 and 01616412
- Volume :
- 44
- Database :
- OpenAIRE
- Journal :
- Neurological Research
- Accession number :
- edsair.doi.dedup.....04f1ad22ba11d672668550866b16357e