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Matrix metalloproteinases activity during the evolution of hypoxic-ischemic brain damage in the immature rat. The effect of 1-methylnicotinamide (MNA)

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Dragun P., Makarewicz D., Wojcik L., Ziemka-Nalecz M., Slomka M., Zalewska T.

Journal of Physiology and Pharmacology

2008

tom 59

nr 3

441-455

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the extracellular matrix and carry out key functions during brain development. Apart from a physiological role, excessive activation of MMPs in brain tissue has been postulated to represent a pathway for cell death arising from ischemia. To evaluate the possible involvement of MMPs in the perinatal brain asphyxia, we exposed 7-day-old rats to hypoxia-ischemia (HI). Unilateral HI was administered by ligation of the common carotid artery followed by hypoxia (7.4% O2/92.6% N2) for 65 minutes. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in > 90% of animals. HI resulted in a significant elevation of MMP-2 and MMP-9 activity in the ipsilateral forebrain. The maximum activation was found at 48 hours and 7-14 days after the insult. These results suggest that early and late induction of MMPs may play a role in neuronal death as well as in repair processes. The treatment of animals subjected to HI with 1-methylnicotinamide (MNA), the anti-inflammatory agent, led to the inhibition of MMP-9 in an acute phase of ischemic damage and to the activation of MMP-2 in the later stages after injury. The timing of MMPs modulation by MNA may indicate its possible therapeutic implications.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Dragun P.

1 Makarewicz D.

1 Slomka M.

1 Wojcik L.

1 Zalewska T.

1 Ziemka-Nalecz M.

1 2008

Wyniki wyszukiwania

Matrix metalloproteinases activity during the evolution of hypoxic-ischemic brain damage in the immature rat. The effect of 1-methylnicotinamide (MNA)