Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema

Hussain, Rashad; Tithof, Jeffrey; Wang, Wei; Cheetham-West, Arokoruba; Song, Wei; Peng, Weiguo; Sigurdsson, Björn; Kim, Daehyun; Sun, Qian; Peng, Sisi; Plá, Virginia; Kelley, Douglas H.; Hirase, Hajime; Castorena-Gonzalez, Jorge A.; Weikop, Pia; Goldman, Steven A.; Davis, Michael J.; Nedergaard, Maiken

doi:10.1038/s41586-023-06737-7

Cited by 48 publications

(37 citation statements)

References 61 publications

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“…The glymphatic system plays a crucial role in the physiological and pathological processes of the CNS, including immune surveillance and inflammatory response. 6,10,36 Our study has revealed that an ultraearly therapeutic hypothermia strategy aimed at enhancing the glymphatic influx following brain injury in mice could facilitate the upregulation of genes implicated in brain tissue repair. This strategy also con- currently suppresses cellular immune-related pathways while promoting humoral immune-related pathways.…”

Section: Discussionmentioning

confidence: 95%

“…Several studies have shown that the glymphatic system plays a crucial role in the immune inflammatory response of various CNS diseases. ,, The profitability of early prophylactic hypothermia in patients with brain injury has been a subject of ongoing debate . The regularity of the glymphatic influx regulation by hypothermia suggests that we need to review hypothermia’s impact on immune inflammation following brain injury.…”

Section: Resultsmentioning

confidence: 99%

“…The peripheral lymphatic system of vertebrates serves as the primary pathway for eliminating metabolic waste and excess fluid, playing crucial roles in maintaining fluid balance, immune surveillance, and lipid reabsorption . While the brain exhibits high energy consumption and metabolism characteristics, it is traditionally believed to lack a lymphatic system and enjoy the “immune privilege.” Recent studies have revealed the existence of a specialized lymphatic transport system of the central nervous system (CNS), known as the glymphatic system. , Cerebrospinal fluid (CSF) assumes the role of lymphatic fluid in the CNS, participating in solute transport, metabolite clearance, and immunoinflammatory response. − The involvement of the glymphatic system is observed in various CNS disease processes such as brain tumors, stroke, brain injury, and degenerative diseases. ,− Targeting the glymphatic system may offer effective therapeutic strategies for most CNS diseases.…”

Section: Introductionmentioning

confidence: 99%

“…During natural sleep, the glymphatic system is more active and effectively clears metabolic waste from the brain . Several sleep-related factors, such as circadian rhythms, sympathetic nerve tension, and endogenous sleep factors, have been shown to regulate this system. ,, However, it is unclear whether core body temperature (CBT), a marker of circadian pacing regulation of sleep, regulates the glymphatic system. Moreover, changes in physiological parameters, such as arterial pulsation, heart rate, and blood pressure, can affect the glymphatic influx. ,,, Animals experience a lower CBT and reduced respiratory and heart rates during sleep .…”

Section: Introductionmentioning

confidence: 99%

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Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx

Li,

Sun,

Zhang

et al. 2024

ACS Nano

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Advanced in vivo imaging techniques have facilitated the comprehensive visual exploration of animal biological processes, leading to groundbreaking discoveries such as the glymphatic system. However, current limitations of macroscopic imaging techniques impede the precise investigation of physiological parameters regulating this specialized lymphatic transport system. While NIR-II fluorescence imaging has demonstrated advantages in peripheral lymphatic imaging, there are few reports regarding its utilization in the glymphatic system. To address this, a noninvasive transcranial macroscopic NIR-II fluorescence imaging model is developed using a cyanine dye-protein coupled nanoprobe. NIR-II imaging with high temporal and spatial resolution reveals that hypothermia can increase the glymphatic influx by reducing the flow rate of cerebrospinal fluid. In addition, respiratory rate, respiratory amplitude, and heart rate all play a role in regulating the glymphatic influx. Thus, targeting the glymphatic influx may alter the trajectory of immune inflammation following brain injury, providing therapeutic prospects for treating brain injury with mild hypothermia.

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Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx

Li,

Sun,

Zhang

et al. 2024

ACS Nano

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show abstract

“…Many relevant questions remain unexplored and warrant attention in future studies. For instance, during the acute phase, slow waves may initially be neuroprotective contributing to anatomical reorganization through axonal sprouting [52], reducing metabolic costs, alleviating excitotoxicity, and mitigating extracellular compartment alterations [53,54] particularly in perilesional areas. Complementing our findings with longitudinal measurements encompassing the acute phase will therefore be pivotal in elucidating the intricate interactions between slow waves and their consequences across various disease stages.…”

Section: Outstanding Questions and Future Directionsmentioning

confidence: 99%

The reduction of sleep-like perilesional cortical dynamics underlies clinical recovery in stroke

Sarasso,

D’Ambrosio,

Russo

et al. 2024

Preprint

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Introduction. Recent studies have shown that, following brain injury, sleep-like cortical dynamics intrude into wakefulness, potentially contributing to brain network disruption and behavioral deficits. Aim. We employ TMS in combination with EEG to detect these dynamics and assess their impact on brain networks and clinical evolution in awake stroke patients. Methods. Twelve patients with subacute unilateral ischemic cortical stroke underwent a longitudinal study with two assessments (t0 and t1), including clinical evaluation using the National Institutes of Health Stroke Scale (NIHSS) and TMS-EEG recordings targeting perilesional and contralesional cortical sites. Parameters such as slow wave amplitude (SWa), high-frequency power (HFp) suppression, and the Perturbational Complexity Index-state transition (PCIst) were analyzed to quantify sleep-like cortical dynamics and their network-level consequences. Results. Results demonstrated a significant clinical improvement (NIHSS score: 7.16 +/- 0.73 at t0, 4.33 +/- 0.74 at t1; W=78, P<0.001). Perilesional SWa and HFp suppression decreased significantly at t1 compared to t0 (T(11)=3.05, P=0.01 and T(11)=-3.39, P<0.01, respectively), along with recovery of PCIst values (T(11)=-2.35, P=0.04). Importantly, both the dissipation of sleep-like perilesional cortical dynamics and the recovery of network-level interactions correlated with patients' clinical improvement (Spearman rho=0.62, P=0.03; rho=-0.68, P=0.01, respectively). Conclusion. These findings underscore the potential of TMS-EEG as an objective measure of neurological evolution and suggest targeting sleep-like cortical dynamics as a viable strategy for post-stroke neuromodulation and rehabilitation.

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A Self‐Gelling Powder Directly Co‐Assembled by Natural Small Molecules for Traumatic Brain Injury

Yang,

Luo,

Song

et al. 2024

Adv Funct Materials

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The prognosis for traumatic brain injury (TBI) depends largely on prompt hemostasis and effective pharmacologic interventions. Natural all‐small‐molecule self‐gelling powder, integrating the advantages of self‐assembled small‐molecule hydrogels and powders, is expected to provide timely and effective prehospital management of TBI. However, the synthesis and application of natural all‐small‐molecule self‐gelling powder is still uncharted territory. In this study, an all‐small‐molecule co‐assembled MGF‐H3BO3‐RUT (MBR) self‐gelling powder is fabricated through the co‐assembly of mangiferin (MGF) and rutin (RUT) in H3BO3/NaOH aqueous solution. Both compounds can bind with boric acid, leading to co‐assembling into hydrogels through hydrogen‐bonding interactions and π–π stacking. MBR self‐gelling powder is then obtained by drying the as‐prepared hydrogels, thus integrating hemostasis and pharmacodynamics into one. Remarkably, it displays robust regeneration capabilities, while retaining excellent self‐healing properties and injectability after drying‐hydration cycles. Moreover, MBR self‐gelling powder not only achieves rapid effective hemostasis but also attenuates conspicuously cerebral edema and inflammatory response after TBI by in situ spraying, exhibiting notable neuroprotective effects without discernible toxic side effects. This study provides a novel assembly strategy and application form for self‐assembled gel materials originating from natural small molecules, offering promising avenues for the treatment of TBI in the acute phase.

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Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema

Cited by 48 publications

References 61 publications

Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx

Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx

The reduction of sleep-like perilesional cortical dynamics underlies clinical recovery in stroke

A Self‐Gelling Powder Directly Co‐Assembled by Natural Small Molecules for Traumatic Brain Injury

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