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. 2014:2014:586501.
doi: 10.1155/2014/586501. Epub 2014 Mar 20.

Cerebrovascular and neuroprotective effects of adamantane derivative

Ruben S Mirzoyan  1 , Tamara S Gan'shina  1 , Denis V Maslennikov  1 , Georgy I Kovalev  1 , Ivan A Zimin  1 , Boris M Pyatin  1 , Nina I Avdyunina  1 , Anna M Kukhtarova  1 , Nelly G Khostikyan  2 , Vahe S Meliksetyan  2 , Cristina B Alikhanyan  2 , Narine R Mirzoyan  2
Affiliations

Cerebrovascular and neuroprotective effects of adamantane derivative

Ruben S Mirzoyan et al. Biomed Res Int. 2014.

Abstract

Objectives: The influence of 5-hydroxyadamantane-2-on was studied on the rats' brain blood flow and on morphological state of brain tissue under the condition of brain ischemia. The interaction of the substance with NMDA receptors was also studied.

Methods: Study has been implemented using the methods of local blood flow registration by laser flowmeter, [(3)H]-MK-801binding, and morphological examination of the brain tissue. We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, and hypergravity ischemia of the brain.

Results: Unlike memantine, antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not block NMDA receptors but enhances the cerebral blood flow of rats with brain ischemia. This effect is eliminated by bicuculline. Under conditions of permanent occlusion of middle cerebral artery, 5-hydroxyadamantane-2-on has recovered compensatory regeneration in neural cells, axons, and glial cells, and the number of microcirculatory vessels was increased. 5-Hydroxyadamantane-2-on was increasing the survival rate of animals with hypergravity ischemia.

Conclusions: 5-Hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist, demonstrates significant cerebrovascular and neuroprotective activity in conditions of brain ischemia. Presumably, the GABA-ergic system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-hydroxyadamantane-2-on.

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Figures

Figure 1
Figure 1
The influence of 5-hydroxyadamantane-2-on (100 mg/kg, IV) on CBF of intact rats (a) and animals with global transient brain ischemia (b).
Figure 2
Figure 2
The influence of 5-hydroxyadamantane-2-on (100 mg/kg, IV) (5HA-2-on) on local cerebral blood (CBF), blood pressure (BP), and rated resistance (RR) of rats after global transient ischemia of the brain (a) and with action of bicuculline (b).
Figure 3
Figure 3
Morphological picture of brain tissue of rats with occlusion of middle cerebral artery. (a) An expressed perivascular and pericellular edema of the brain, stasis in arterioles, and foci of empty neural and glial cells (staining hematoxylin/eosin ×400). (b) Against the background of necrobiosis, anuclear shadow cells of neurons as well as dystrophic neural and glial cells are seen (staining hematoxylin/eosin ×400).
Figure 4
Figure 4
Morphological picture of brain tissue of rats with occlusion of middle cerebral artery after treatment with 5-hydroxyadamantane-2-on. (a) Hypertrophic pyramidal cells with preserved neuritis (staining hematoxylin/eosin ×400); (b) along with hypertrophic cells, those without axons and with wrinkled cytoplasm and nucleus are seen (staining hematoxylin/eosin ×400).
Figure 5
Figure 5
Morphological picture of brain tissue of rats with occlusion of middle cerebral artery after treatment with 5-hydroxyadamantane-2-on. Lymphoid-macrophagal reaction is observed in zones of necrosis and marked edema in response to impaired polycystic changes of brain tissue (staining hematoxylin/eosin ×400).
Figure 6
Figure 6
The influence of memantine and 5-hydroxyadamantane-2-on on specific binding of [3H]-MK-801 with rat hippocampal membranes (pIC50 = m ± S.E.).
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