Dynamic Measurements of Cerebral Blood Flow Responses to Cortical Spreading Depolarization in the Murine Endovascular Perforation Subarachnoid Hemorrhage Model

Jin, Yan; Li, Wenlang; Zhou, Chao; Wu, Na; Yang, Xiaomin; Pan, Qiuling; He, Tao; Wu, Yue; Guo, Zongduo; Xia, Yongzhi; Sun, Xiaochuan; Cheng, Chung–Ying

doi:10.1007/s12975-022-01052-1

Cited by 6 publications

(4 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To assess the CBF changes after CCI, we used a laser speckle contrast imaging (LSCI) system (Peri-Cam PSI System; Perimed) [ 39 ]. After deep anaesthetization, the head was fixed in a stereotaxic frame (RWD Life Science Co., Ltd, Shenzhen, China), and the eyes were coated with erythromycin eye ointment.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

TREM2 activation alleviates neural damage via Akt/CREB/BDNF signalling after traumatic brain injury in mice

Jin

Zhang

Wang

et al. 2022

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

Background Neuroinflammation is one of the most important processes in secondary injury after traumatic brain injury (TBI). Triggering receptor expressed on myeloid cells 2 (TREM2) has been proven to exert neuroprotective effects in neurodegenerative diseases and stroke by modulating neuroinflammation, and promoting phagocytosis and cell survival. However, the role of TREM2 in TBI has not yet been elucidated. In this study, we are the first to use COG1410, an agonist of TREM2, to assess the effects of TREM2 activation in a murine TBI model. Methods Adult male wild-type (WT) C57BL/6 mice and adult male TREM2 KO mice were subjected to different treatments. TBI was established by the controlled cortical impact (CCI) method. COG1410 was delivered 1 h after CCI via tail vein injection. Western blot analysis, immunofluorescence, laser speckle contrast imaging (LSCI), neurological behaviour tests, brain electrophysiological monitoring, Evans blue assays, magnetic resonance imaging (MRI), and brain water content measurement were performed in this study. Results The expression of endogenous TREM2 peaked at 3 d after CCI, and it was mainly expressed on microglia and neurons. We found that COG1410 improved neurological functions within 3 d, as well as neurological functions and brain electrophysiological activity at 2 weeks after CCI. COG1410 exerted neuroprotective effects by inhibiting neutrophil infiltration and microglial activation, and suppressing neuroinflammation after CCI. In addition, COG1410 treatment alleviated blood brain barrier (BBB) disruption and brain oedema; furthermore, COG1410 promoted cerebral blood flow (CBF) recovery at traumatic injury sites after CCI. In addition, COG1410 suppressed neural apoptosis at 3 d after CCI. TREM2 activation upregulated p-Akt, p-CREB, BDNF, and Bcl-2 and suppressed TNF-α, IL-1β, Bax, and cleaved caspase-3 at 3 d after CCI. Moreover, TREM2 knockout abolished the effects of COG1410 on vascular phenotypes and microglial states. Finally, the neuroprotective effects of COG1410 were suppressed by TREM2 depletion. Conclusions Altogether, we are the first to demonstrate that TREM2 activation by COG1410 alleviated neural damage through activation of Akt/CREB/BDNF signalling axis in microglia after CCI. Finally, COG1410 treatment improved neurological behaviour and brain electrophysiological activity after CCI. Graphical Abstract

show abstract

Section: Methodsmentioning

confidence: 99%

“…We used power spectral density (PSD) analysis for continuous variables to calculate the PSD of theta oscillations (4–12 Hz). The area under curve (AUC) represents the sum PSD of theta oscillations [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

TREM2 activation alleviates neural damage via Akt/CREB/BDNF signalling after traumatic brain injury in mice

Jin

Zhang

Wang

et al. 2022

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another interesting point is that inverse (vasoconstrictive) rCBF responses can be triggered not only by SDs in aSAH patients [20,21], in animal models mimicking conditions after aSAH [34,63,72,78,[106][107][108][109][110] and after experimental SAH [97]. Rather, they can also be triggered by (1) electrographic seizures in aSAH patients [111], and, Fig.…”

Section: Possible Mechanisms Of Inverse Hemodynamic Responsesmentioning

confidence: 97%

“…Typical rodent models of experimental SAH use cisternal injection of blood or vessel puncture and convincingly replicate the evolution of angiographic vasospasm, but fail to replicate the characteristic clinical course of delayed infarcts in patients [94]. Accordingly, the cisternal injection model of blood in mice did not result in SDs either [95], and endovascular puncture failed to show spontaneous SDs in the delayed phase [96,97]. The limitation of rodent models for DCI is that thick subarachnoid blood clots on admission CT scans are consistently among the most important predictors of delayed infarcts [3,[10][11][12][13][14][15], but the small lissencephalic brains of rodents, unlike the larger gyrencephalic brains of non-human primates, swine, and dogs, do not permit thick subarachnoid clots required for infarction.…”

Section: Animal Models Of Eci and DCImentioning

confidence: 99%

All Three Supersystems—Nervous, Vascular, and Immune—Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage

Dreier,

Joerk,

Uchikawa

et al. 2024

Transl. Stroke Res.

View full text Add to dashboard Cite

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical infarcts are caused by acute severe vasospastic events, so-called spreading ischemia, triggered by spontaneously occurring spreading depolarization. In locations where a spreading depolarization passes through, cerebral blood flow can drastically drop within a few seconds and remain suppressed for minutes or even hours, often followed by high-amplitude, sustained hyperemia. In spreading depolarization, neurons lead the event, and the other cells of the neurovascular unit (endothelium, vascular smooth muscle, pericytes, astrocytes, microglia, oligodendrocytes) follow. However, dysregulation in cells of all three supersystems—nervous, vascular, and immune—is very likely involved in the dysfunction of the neurovascular unit underlying spreading ischemia. It is assumed that subarachnoid blood, which lies directly on the cortex and enters the parenchyma via glymphatic channels, triggers these dysregulations. This review discusses the neuroglial, neurovascular, and neuroimmunological dysregulations in the context of spreading depolarization and spreading ischemia as critical elements in the pathogenesis of cortical infarcts after subarachnoid hemorrhage.

show abstract

How to Promote Hemoglobin Scavenging or Clearance and Detoxification in Hemorrhagic Stroke

Suzuki

2022

Transl. Stroke Res.

View full text Add to dashboard Cite

Dynamic Measurements of Cerebral Blood Flow Responses to Cortical Spreading Depolarization in the Murine Endovascular Perforation Subarachnoid Hemorrhage Model

Cited by 6 publications

References 56 publications

TREM2 activation alleviates neural damage via Akt/CREB/BDNF signalling after traumatic brain injury in mice

TREM2 activation alleviates neural damage via Akt/CREB/BDNF signalling after traumatic brain injury in mice

All Three Supersystems—Nervous, Vascular, and Immune—Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage

How to Promote Hemoglobin Scavenging or Clearance and Detoxification in Hemorrhagic Stroke

Contact Info

Product

Resources

About