Investigating recovery after a spontaneous intracerebral haemorrhage in zebrafish larvae.

IF 4.1 Q1 CLINICAL NEUROLOGY
Brain communications Pub Date : 2024-09-12 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae310
Siobhan Crilly, Isabel Shand, Abigail Bennington, Emily McMahon, Daisy Flatman, Victor S Tapia, Paul R Kasher
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Abstract

Intracerebral haemorrhage is a debilitating stroke sub-type with high morbidity and mortality rates. For survivors, rehabilitation is a long process, and with no available therapeutics to limit the immediate pathophysiology of the haemorrhage, recovery is dependent on individual neuroplasticity. We have previously shown that zebrafish larvae can be used to model spontaneous brain haemorrhage. Zebrafish exhibit innate recovery mechanisms and are often used as a model system for investigation into regeneration after injury, including injury to the nervous system. Here, we investigate the spontaneous and immediate recovery in zebrafish larvae following an intracerebral haemorrhage at 2 days post-fertilisation, during pre-protected stages and over the first 3 weeks of life. We have shown that following the onset of bleed at ∼2 days post-fertilisation zebrafish are capable of clearing the haematoma through the ventricles. Brain cell damage associated with intracerebral haemorrhage is resolved within 48 h, and this recovery is associated with survival rates equal to wildtype and non-haemorrhaged sibling control animals. Larvae express more nestin-positive neural progenitor cells 24 h after injury when the most damage is observed, and through mass spectrometry analysis, we have determined that these cells are highly proliferative and may specially differentiate into oligodendrocytes. This study provides an insight into the haematoma resolution processes in a live, intact organism, and may suggest potential therapeutic approaches to support the recovery of intracerebral haemorrhage patients.

研究斑马鱼幼体自发性脑内出血后的恢复情况。
脑出血是一种使人衰弱的中风亚型,发病率和死亡率都很高。对于幸存者来说,康复是一个漫长的过程,由于没有可用的治疗方法来限制出血的直接病理生理学,康复取决于个体的神经可塑性。我们之前已经证明,斑马鱼幼体可以用来模拟自发性脑出血。斑马鱼表现出与生俱来的恢复机制,经常被用作研究损伤后再生(包括神经系统损伤)的模型系统。在此,我们研究了斑马鱼幼体在受精后 2 天、保护前阶段和出生后前 3 周脑出血后的自发和即时恢复情况。我们已经证明,在受精后 2 天出血开始后,斑马鱼能够通过脑室清除血肿。与脑内出血相关的脑细胞损伤可在 48 小时内消除,这种恢复与野生型和未出血的同胞对照动物的存活率相同。幼体在损伤后 24 小时表达更多的 nestin 阳性神经祖细胞,此时观察到的损伤最为严重,通过质谱分析,我们确定这些细胞具有高度增殖性,并可能专门分化为少突胶质细胞。这项研究让我们深入了解了活体完整生物体的血肿消解过程,并为支持脑内出血患者的康复提供了潜在的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.00
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0.00%
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审稿时长
6 weeks
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