Moderate systemic therapeutic hypothermia is insufficient to protect blood-spinal cord barrier in spinal cord injury

Zhou, Rubing; Li, Junzhao; Wang, Ruideng; Chen, Zhengyang; Zhou, Fang

doi:10.3389/fneur.2022.1041099

Cited by 3 publications

(3 citation statements)

References 67 publications

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“…Therefore, further research is needed to develop diagnostic and predictive prognostic models for acute TSCI, and a framework for identifying valuable biomarkers is also necessary to improve the accuracy of prognostic prediction. It has been shown that the blood-spinal cord barrier (BSCB) is disrupted by TSCI, leukocyte tra cking is also increased (21,22). Some in ammatory biomarkers, such as C-reactive protein (CRP ), IL-6 or monocyte chemotactic protein-1, can participate in the systemic in ammatory response and can be transported into the blood or cerebrospinal uid(8, 23,24).…”

Section: Discussionmentioning

confidence: 99%

Serum glucose/potassium ratio as a clinical risk factor for predicting the severity and prognosis of acute traumatic spinal cord injury

Zhou,

Liu,

Wang

et al. 2023

Preprint

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Objective Acute traumatic spinal cord injury (TSCI) can lead to poor prognosis, and clinical biomarkers have not been established to predict poor prognosis. This study aimed to determine the significance of serum glucose/potassium ratio (GPR) in evaluating TSCI severity and predicting prognosis. Methods An analysis of 520 clinical records of acute TSCI patients from January 2012 to June 2022 was conducted by the authors. The relationship between serum GPR and The American Spinal Injury Association Impairment Scale (AIS) grade 6-month post-trauma prognosis in addition to admission AIS grade was analyzed. In order to evaluate the discriminatory ability, a receiver operating characteristic curve was used. All methods were performed in accordance with the relevant guidelines and regulations. Results Based on the initial assessment of AIS grade, 256 (49.2%) patients were categorized into the severe TSCI group (AIS A-B), and there was a significant correlation between the severe TSCI group and serum GPR (p < 0.001). Serum GPR was reduced in an AIS grade-dependent manner (R=-0.540, p < 0.001). 262 (50.4%) patients were classified as poor prognosis according to the AIS grade at discharge. Serum GPR was also reduced in AIS grade in a discharge-dependent manner (R = -0.599, p < 0.001). It was significantly higher in the poor prognosis group compared to the good prognosis group (p < 0.001 ). Poor prognosis was significantly associated with sex(p = 0.009), severity of TSCI (p < 0.001), location of TSCI (p < 0.001), Surgical decompression(P < 0.018), body temperature (p < 0.001), heart rate (p < 0.001), systolic arterial pressure (SAP) (p < 0.001), diastolic arterial pressure (DAP) (p < 0.001), serum GPR (p < 0.001), serum glucose (p < 0.001), serum potassium (p < 0.001) and white blood cell (WBC) count (p = 0.003). Multivariate logistic regression analysis showed a significant correlation between poor prognosis and serum GPR (p = 0.023). The ROC analysis showed that the area under the curve (AUC) of serum GPR as a poor predictor of prognosis in TSCI patients was 0.842 (95% CI 0.808–0.875). Conclusion There was a significant relationship between serum GPR and admission injury severity and 6-month prognosis of acute TSCI patients. The serum GPR can be used to assess the severity of acute TSCI and predict the prognosis .

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Section: Discussionmentioning

confidence: 99%

Serum glucose/potassium ratio as a clinical risk factor for predicting the severity and prognosis of acute traumatic spinal cord injury

Zhou,

Liu,

Wang

et al. 2023

Preprint

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“…Our data suggest that the protective effect of CHA on blood–brain barrier integrity is likely the main mechanism underlying its protection against neuroinflammation. Previous studies have indicated that hyperthermia increases BBB permeability, while therapeutic hypothermia can have a protective effect [ 18 , 19 , 20 , 21 , 22 ]. Consistent with the literature, our data also confirm that CHA-induced hypothermia significantly prevents the loss of zo-1, preserving blood–brain barrier integrity.…”

Section: Discussionmentioning

confidence: 99%

Torpor-like Hypothermia Induced by A1 Adenosine Receptor Agonist: A Novel Approach to Protect against Neuroinflammation

Hui

Wang

et al. 2023

IJMS

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Hypothermia is a promising clinical therapy for acute injuries, including neural damage, but it also faces practical limitations due to the complexities of the equipment and procedures required. This study investigates the use of the A1 adenosine receptor (A1AR) agonist N6-cyclohexyladenosine (CHA) as a more accessible method to induce steady, torpor-like hypothermic states. Additionally, this study investigates the protective potential of CHA against LPS-induced sepsis and neuroinflammation. Our results reveal that CHA can successfully induce a hypothermic state by activating a neuronal circuit similar to the one that induces physiological torpor. This state is characterized by maintaining a steady core body temperature below 28 °C. We further found that this torpor-like state effectively mitigates neuroinflammation and preserves the integrity of the blood–brain barrier during sepsis, thereby limiting the infiltration of inflammatory factors into the central nervous system. Instead of being a direct effect of CHA, this protective effect is attributed to inhibiting pro-inflammatory responses in macrophages and reducing oxidative stress damage in endothelial cells under systemic hypothermia. These results suggest that A1AR agonists such as CHA could potentially be potent neuroprotective agents against neuroinflammation. They also shed light on possible future directions for the application of hypothermia-based therapies in the treatment of sepsis and other neuroinflammatory conditions.

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“…Endothelial cells (ECs) play a key role in regulating selective transport and metabolic exchange between the blood and the spinal cord as a vital component of the BSCB (12). Post-SCI, ECs undergo regeneration at the site of injury; however, their functional attributes are markedly diminished relative to their healthy counterparts, spanning diminished barrier functionality to compromised substance transport (13,14).…”

Section: Introductionmentioning

confidence: 99%

MCT1-Mediated Endothelial Cell Lactate Shuttle as a Target for Promoting Axon Regeneration after Spinal Cord Injury

Shi,

Xu,

Ding

et al. 2024

Preprint

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Vascular damage following spinal cord injury (SCI) precipitates ischemia and hypoxia at the injury site, leading to profound metabolic disturbances. The implications of these metabolic disorders on neural tissue remodeling and functional recovery remain poorly understood. Our study elucidates the consequences of the hypoxic environment induced by SCI, which significantly enhances glycolysis and lactate production at the injury's epicenter. And our findings revealed a marked decrease in the expression of Monocarboxylate Transporter 1 (MCT1), a crucial transporter facilitating lactate delivery to neurons and consequently supporting their energy metabolism, within vascular endothelial cells emerging after SCI. This decrease disrupts lactate transport to neurons, resulting in metabolic imbalances that impede axonal regeneration. Remarkably, our research demonstrates that targeted delivery of adeno-associated virus (AAV) injections to restore MCT1 expression in endothelial cells (ECs) promotes axonal regeneration and functional recovery in SCI mouse models. These findings reveal a previously unrecognized connection between lactate shuttling from ECs to neurons after SCI and neural functional recovery. Highlighting a novel metabolic pathway for intervention, our study opens new therapeutic avenues for the treatment of spinal cord injuries, suggesting that targeting lactate transport mechanisms may offer significant benefits in SCI recovery.

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Moderate systemic therapeutic hypothermia is insufficient to protect blood-spinal cord barrier in spinal cord injury

Cited by 3 publications

References 67 publications

Serum glucose/potassium ratio as a clinical risk factor for predicting the severity and prognosis of acute traumatic spinal cord injury

Serum glucose/potassium ratio as a clinical risk factor for predicting the severity and prognosis of acute traumatic spinal cord injury

Torpor-like Hypothermia Induced by A1 Adenosine Receptor Agonist: A Novel Approach to Protect against Neuroinflammation

MCT1-Mediated Endothelial Cell Lactate Shuttle as a Target for Promoting Axon Regeneration after Spinal Cord Injury

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