Preventive Effects of Neuroprotective Agents in a Neonatal Rat of Photothrombotic Stroke Model.

Yoon Young Yi,Sung Koo Kim,Dong Woon Kim,Hyo Jung Shin,Seung Gyu Choi,Hee-Jung Song,Joon Won Kang

doi:10.3390/ijms21103703

Abstract

Neonatal ischemic stroke has a higher incidence than childhood stroke. Seizures are the first sign for the need for clinical assessment in neonates, but many questions remain regarding treatments and follow-up modalities. In the absence of a known pathophysiological mechanism, only supportive care is currently provided. Stroke-induced microglia activation and neuroinflammation are believed to play a central role in the pathological progression of neonatal ischemic stroke. We induced a photothrombotic infarction with Rose Bengal in neonatal rats to investigate the effects of pre- and post-treatment with Aspirin (ASA), Clopidogrel (Clop), and Coenzyme Q10 (CoQ10), which are known for their neuroprotective effects in adult stroke. Pre-stroke medication ameliorates cerebral ischemic injury and reduces infarct volume by reducing microglia activation, cellular reactive oxygen species (ROS) production, and cytokine release. Post-stroke administration of ASA, Clop, and CoQ10 increased motor function and reduced the volume of infarction, and the statistical evidence was stronger than that seen in the pre-stroke treatment. In this study, we demonstrated that ASA, Clop, and CoQ10 treatment before and after the stroke reduced the scope of stroke lesions and increased behavioral activity. It suggests that ASA, Clop, and CoQ10 medication could significantly have neuroprotective effects in the neonates who have suffered strokes.

Highlights

Pediatric ischemic stroke occurs more frequently in neonates with the incidence of 1 per 4000 live births, compared to childhood incidence of 1 per 100,000 children [1]
We investigated the effects of commonly used and possibly neuroprotective medication, acetylsalicylic acid (ASA; Aspirin), clopidogrel (Clop), and Coenzyme Q10 (CoQ10, ubiquinone, ubidecarenone) in Rose Bengal (RB)-induced photothrombosis in neonatal rats
Focal Ischemic Stroke in Neonatal Rat Induced by Photothrombosis

Summary

Introduction

Pediatric ischemic stroke occurs more frequently in neonates with the incidence of 1 per 4000 live births, compared to childhood incidence of 1 per 100,000 children [1]. Thrombolytic therapy within 3 h of the onset of stroke symptoms is the most effective therapeutic approach for acute stroke management in over two-year-old patients [2], but not for neonates. This is due to complications and high mortality after treatment and relatively lower recurrence rates (1.2–2.8%) [3,4] than other age groups (20–30%) [5]. Neonates with high-risk factors such as congenital heart disease may still have recurrent stroke, and cardiac disorders are associated with 10% to 30% of strokes in children [6,7]

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