Eastern Kentucky University

Poster Title

Neuroprotective Effects of Hydrogen Sulfide Through the NMDA Receptor Against Intracerebral Homocysteine Induced BBB Dysfunction and Vascular Remodeling

Institution

Eastern Kentucky University

Abstract

The disruption and subsequent irregularity of the blood brain barrier (BBB) leads to an abnormal cerebral blood flow (CBF) and dramatically affects neuronal toxicity and cognitive impairment. Homocysteine (Hcy) is a known aggravator in this process by causing the over activation of the NMDA receptor. The over activation of the NMDA receptor creates excitotoxicity impart by BBB disruption and hippocampal neurotoxicity. Hydrogen sulfide can be used to alleviate the effects of homocysteine by facilitating hippocampal long-term potentiation. Therefore, the present study was designed to study the effect of Hcy (0.5μg/ μl) induced NMDA receptor activation on BBB integrity, CBF, memory function, and determine if hydrogen sulfide can attenuate the associated negative effects. Our results suggest that Hcy administration (IC) resulted in altered CBF BBB permeability, depressive behaviors, memory function, and blood pressure. In our experiment, sodium hydrogen sulfide (H2S donor) and MK801 (NMDA antagonist) were injected intraperitoneally once daily for a period of 7 days after Hcy treatment. Pretreated groups with NaHS (30μM/kg) and MK801 (0.05mg/kg) showed improved memory formation as evaluated by recognition tests, CBF, and BBB permeability. In terms of hippocampal alteration, we observed changes in protein and mRNA expression levels of the following: NR1, GFAP, eNOS, ICAM-1, SAP97, PSD95, BDNF, NOX, and MMPs. The present study clearly demonstrates that Hcy (IC) induces altered BBB integrity and CBF which is related to memory impairment and hippocampal toxicity and more importantly that NaHS and MK801 treatments can help ameliorate homocysteine’s negative effects.

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Neuroprotective Effects of Hydrogen Sulfide Through the NMDA Receptor Against Intracerebral Homocysteine Induced BBB Dysfunction and Vascular Remodeling

The disruption and subsequent irregularity of the blood brain barrier (BBB) leads to an abnormal cerebral blood flow (CBF) and dramatically affects neuronal toxicity and cognitive impairment. Homocysteine (Hcy) is a known aggravator in this process by causing the over activation of the NMDA receptor. The over activation of the NMDA receptor creates excitotoxicity impart by BBB disruption and hippocampal neurotoxicity. Hydrogen sulfide can be used to alleviate the effects of homocysteine by facilitating hippocampal long-term potentiation. Therefore, the present study was designed to study the effect of Hcy (0.5μg/ μl) induced NMDA receptor activation on BBB integrity, CBF, memory function, and determine if hydrogen sulfide can attenuate the associated negative effects. Our results suggest that Hcy administration (IC) resulted in altered CBF BBB permeability, depressive behaviors, memory function, and blood pressure. In our experiment, sodium hydrogen sulfide (H2S donor) and MK801 (NMDA antagonist) were injected intraperitoneally once daily for a period of 7 days after Hcy treatment. Pretreated groups with NaHS (30μM/kg) and MK801 (0.05mg/kg) showed improved memory formation as evaluated by recognition tests, CBF, and BBB permeability. In terms of hippocampal alteration, we observed changes in protein and mRNA expression levels of the following: NR1, GFAP, eNOS, ICAM-1, SAP97, PSD95, BDNF, NOX, and MMPs. The present study clearly demonstrates that Hcy (IC) induces altered BBB integrity and CBF which is related to memory impairment and hippocampal toxicity and more importantly that NaHS and MK801 treatments can help ameliorate homocysteine’s negative effects.