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SIRT1 Activation Promotes Long-Term Functional Recovery After Subarachnoid Hemorrhage in Rats

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Abstract

Background

An increase in sirtuin 1 (SIRT1) reportedly attenuates early brain injury, delayed cerebral ischemia, and short-term neurologic deficits in rodent models of subarachnoid hemorrhage (SAH). This study investigates the effect of resveratrol, a SIRT1 activator, on long-term functional recovery in a clinically relevant rat model of SAH.

Methods

Thirty male Wistar rats were subjected to fresh arterial blood injection into the prechiasmatic space and randomized to receive 7 days of intraperitoneal resveratrol (20 mg/kg) or vehicle injections. Body weight and rotarod performance were measured on days 0, 3, 7, and 34 post SAH. The neurologic score was assessed 7 and 34 days post SAH. Morris water maze performance was evaluated 29–33 days post SAH. Brain SIRT1 activity and CA1 neuronal survival were also assessed.

Results

Blood pressure rapidly increased in all SAH rats, and no between-group differences in blood pressure, blood gases, or glucose were detected. SAH induced weight loss during the first 7 days, which gradually recovered in both groups. Neurologic score and rotarod performance were significantly improved after resveratrol treatment at 34 days post SAH (p = 0.01 and 0.04, respectively). Latency to find the Morris water maze hidden platform was shortened (p = 0.02). In the resveratrol group, more CA1 neurons survived following SAH (p = 0.1). An increase in brain SIRT1 activity was confirmed in the resveratrol group (p < 0.05).

Conclusions

Treatment with resveratrol for 1 week significantly improved the neurologic score, rotarod performance, and latency to find the Morris water maze hidden platform 34 days post SAH. These findings indicate that SIRT1 activation warrants further investigation as a mechanistic target for SAH therapy.

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Funding

This project was funded by US Public Health Service National Institutes of Health grant 1R01NS091603 (principal investigator: GJZ).

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Author notes

  1. Dongmei Chu and Xuan Li have contributed equally to this work.

Authors and Affiliations

  1. Multidisciplinary Neuroprotection Laboratories, Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA

    Dongmei Chu, Xuan Li, Xingguang Qu, David S. Warner & Huaxin Sheng

  2. Department of Pediatrics, The Fifth Central Hospital of Tianjin, Tanggu District, Tianjin, China

    Dongmei Chu

  3. Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

    Xuan Li

  4. Intensive Care Unit, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China

    Xingguang Qu

  5. Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Deepti Diwan & Gregory J. Zipfel

  6. Department of Surgery, Duke University Medical Center, Durham, NC, USA

    David S. Warner

  7. Department of Neurobiology, Duke University Medical Center, Durham, NC, USA

    David S. Warner

Authors
  1. Dongmei Chu
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  2. Xuan Li
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  4. Deepti Diwan
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  7. Huaxin Sheng
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Contributions

DC, XQ, and HS performed animal surgery, treatment, and behavioral tests. XL performed histologic work and collected data. DD performed SIRT1 measurements. DSW and HS performed data analysis. GJZ and DSW received the National Institutes of Health grant. HS, DSW, and GJZ wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Huaxin Sheng.

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Chu, D., Li, X., Qu, X. et al. SIRT1 Activation Promotes Long-Term Functional Recovery After Subarachnoid Hemorrhage in Rats. Neurocrit Care 38, 622–632 (2023). https://doi.org/10.1007/s12028-022-01614-z

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