Written by Yao Min, Chang Chunqi

Editor in charge ︱ Wang Sizhen

Editor︱Yang Binwei

Intracerebral hemorrhage (ICH) has high morbidity and mortality

In August 2022, Chang Chunqi and Zhang Jian's team from the Medical Department of Shenzhen University published a research paper entitled "Modulation of the proteoglycan receptor PTPσ promotes white matter integrity and functional recovery after intracerebral hemorrhage stroke in mice" in the Journal of Neuroinflammation, proposing ISP It can improve the inflammatory response around hematoma, increase white matter integrity and remyelination, and promote the recovery of nerve function after ICH

Cerebral striatal hematoma can cause long-term unilateral sensorimotor and behavioral coordination deficits

Figure 1 ISP promotes long-term sensorimotor behavior recovery after intracerebral hemorrhage

(Source: Yao M et al.

After intracerebral hemorrhage, the immune inflammatory response around the hematoma is rapid, and microglia are activated and secrete a variety of inflammatory factors, which are involved in nerve damage and repair [3]

Figure 2 ISP inhibits PTPσ to improve inflammatory response

(Source: Yao M et al.

In addition to immune-inflammatory changes, the authors also explored the role of ISP on hematoma, striatal and cervical CST white matter integrity

Figure 3 Long-term improvement of white matter integrity in the brain and cervical spinal cord after ICH with ISP treatment

(Source: Yao M et al.
, J Neuroinflammation, 2022)

Figure 4 Morphological changes of the dorsal CST on the injured side of the cervical C5 segment after ICH under transmission electron microscopy

(Source: Yao M et al.
, J Neuroinflammation, 2022)

The recovery of neural function is closely related to the integrity of neural circuits
.

To determine whether ISP administration could restore the integrity of the cerebral cortex and spinal cord neural circuits, the integrity of the sensory pathways was assessed using somatosensory evoked potential (SSEP) (Fig.
5a) [5]
.

At the 8-week time point after ICH injury, ISP significantly increased SSEP amplitude compared with the vehicle group (Fig.
5bf)
.

In addition, anterograde tracing of nerves in the contralateral primary motor cortex M1 using rAAV2/9 virus injection was used to assess the integrity of the descending motor pathways, including the corticospinal and corticospinal tracts (Fig.
6a) [6]
.

At 2 weeks after rAAV2/9 injection, the brain and C5 spinal cord were harvested and the number of labeled axons in the facial nucleus and dorsal CST that crossed the midline into the injured side was quantified to assess the degree of neuroplasticity
.

The authors found that axons crossing the midline were significantly increased in the ISP-administered group compared to the Vehicle group (Fig.
6bd)
.

The above combined behavioral results suggest that ISP promotes the recovery of neural circuits in the cerebral cortex and spinal cord by enhancing neuroplasticity after intracerebral hemorrhage
.

Figure 5 SSEP at week 8 after ICH showed that ISP administration improved nerve conduction

(Source: Yao M et al.
, J Neuroinflammation, 2022)

Figure 6 ISP administration increases motor axonogenesis

(Source: Yao M et al.
, J Neuroinflammation, 2022)

Figure 4 shows that ISP can promote axonal myelination in vivo
.

Next, the authors used an in vitro cell culture model to further explore the effect of ISP on myelination of oligodendrocytes (OLs) [5]
.

The results showed that ISP could not only significantly increase the growth area of ​​OLs but also promote axonal myelination by regulating the Erk/CREB signaling pathway (Fig.
7)
.

Figure 7 ISP promotes oligodendrocyte growth and myelination through Erk/CREB signaling pathway

(Source: Yao M et al.
, J Neuroinflammation, 2022)

Given that ISP treatment improves the inflammatory environment, promotes axonal myelination, and accelerates hematoma resorption, we further explored the mechanisms by which ISP regulates inflammatory responses as well as neurogenesis and apoptosis
.

On the 14th day after intracerebral hemorrhage, proteomic analysis was performed on the brain tissue around the hematoma area of ​​the Vehicle group and ISP group (Fig.
8 a, b), and the expression analysis of various anti-inflammatory and pro-inflammatory factors was carried out, and the ones that were related to the hematoma were screened out.
Nerve regeneration-related proteins, including Cd44, Ctsz, C3, and Lims1,
etc.

Fig.
8 Proteomic analysis of brain tissue around the hematoma in Vehicle group and ISP group after ICH

(Source: Yao M et al.
, J Neuroinflammation, 2022)

Conclusion and discussion, inspiration and prospect This study revealed for the first time that the regulation of the neurotransmembrane protein receptor PTPσ (protein tyrosine phosphatase-sigma) in intracerebral hemorrhage (ICH) can reduce axonal damage and improve the damage by regulating the Erk/CREB molecular signaling pathway It restores the integrity of neural circuits in the central nervous system, thereby promoting the long-term recovery of neural function
.

However, as a preclinical study, the mode of administration can still be improved
.

Intraperitoneal injection of ISP is still an invasive method of drug delivery.
Although it has been shown to cross the blood-brain barrier and enter the central nervous system, the efficiency of the drug to reach the lesion through the blood circulation remains to be verified
.

In conclusion, this study provides a new understanding of the pathophysiology of cerebral hemorrhage, and the application of ISP provides a new strategy for its treatment
.

Original link: https://jneuroinflammation.
biomedcentral.
com/articles/10.
1186/s12974-022-02561-4#Sec17

First author: Dr.
Yao Min (first from left); Corresponding authors: Professor Zhang Jian (middle), Professor Chang Chunqi (first from right)

(Photo provided by: Shenzhen University School of Medicine)

About the author (swipe up and down to read) 

Zhang Jian, professor, professor of the Department of Pharmacy, School of Medicine, Shenzhen University, master tutor
.

Research on tumor stem cell immunotherapy mechanism, peripheral nerve injury regeneration, cerebral ischemia, epilepsy, anxiety and depression, Huntington's disease, neuromuscular disease, pain and other signal transduction mechanisms and their diagnosis and treatment, nerve injury regeneration, tumor stem cell immunotherapy mechanism, etc.
He has conducted systematic and in-depth basic and applied research and published more than 100 SCI papers
.

He has presided over or participated in a number of national, provincial and municipal natural science fund projects
.

Chang Chunqi, Ph.
D.
, professor and doctoral supervisor of School of Biomedical Engineering, School of Medicine, Shenzhen University
.

He is currently a Distinguished Professor of Shenzhen University, Deputy Director of the Clinical Research Center for Neurological Diseases of Shenzhen University, a member of the Cognition and Brain-inspired Computing Committee of the Chinese Society of Cognitive Science, a member of the Artificial Intelligence Committee of the Alzheimer's Disease Prevention Association, and a member of the Guangdong Association for the Prevention and Treatment of Alzheimer's Disease.
Provincial Cognitive Science Association executive director
.

Using neuroelectrophysiology, neuroimaging, neuromodulation, brain-like simulation, artificial intelligence and other means to engage in multi-species, multi-modal, multi-scale neural information processing and decoding and its application in brain cognition, brain disease, brain-computer interface, brain-like smart applications
.

He presided over a number of general projects of the National Natural Science Foundation of China, GRF projects of the Hong Kong Research Grants Council, key projects of the Shenzhen Science and Technology Commission, and horizontal projects of enterprises.
, Shenzhen Peacock Team,
etc.

Published more than 100 SCI academic papers
.

Selected past articles

【1】Mol Neurobiol︱Cao Zigang's research group revealed the molecular mechanism of paamiparib-induced neurodevelopmental defects and cerebral hemorrhage in zebrafish embryos

【2】Cereb Cortex︱Wang Qian/Wang Xiongfei/Luan Guoming team work together to reveal the functional connection between cerebral gray matter heterotopia and neocortex

【3】Sci Adv︱ Zhao Cunyou/Chen Rongqing's team reveals the mechanism of microRNA-induced social and memory abnormalities in mice: miR-501-3p expression deficiency enhances glutamatergic transmission

【4】Sci Adv︱Zhang Yi's research group discovered important neurons that regulate drug addiction behavior

【5】J Infect︱Wang Yifei's team revealed that the highly expressed gene MAMDC2 in Alzheimer's disease microglia positively regulates the innate antiviral response to neurotropic virus infection

【6】Sci Adv︱Xia Kun/Shen Yiping/Guo Hui Reveal the relationship between key regulatory genes of stress granules and neurodevelopmental disorders

【7】Cell Prolif︱Lai Liangxue/Zhang Kun/Zou Qingjian team successfully constructed a technical system for safe and efficient directional induction of motor neurons in vivo

【8】Nat Commun︱Peng Yueqing's team discovered a new brain area that controls non-REM sleep

【9】eClinicalMedicine︱Wang Qing’s team reports Parkinson’s disease dementia related index determination: quantitative EEG, serum metabolism and inflammation

【10】Cell Biosci | Wang Yongjun's research group revealed the molecular mechanism of D-type dopachrome isomerase-mediated inflammatory response in injured spinal cord

Recommended high-quality scientific research training courses

【1】Training course︱R language clinical prediction biomedical statistics special training

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References (swipe up and down to read) 

[1] DA Duricki, S.
Drndarski, M.
Bernanos, T.
Wood, K.
Bosch, Q.
Chen, HD Shine, C.
Simmons, SCR Williams, SB McMahon, DJ Begley, D.
Cash, LDF Moon, Stroke Recovery in Rats after 24-Hour-Delayed Intramuscular Neurotrophin-3 Infusion, Ann Neurol 85(1) (2019) 32-46.

[2] B.
T.
Lang, J.
M.
Cregg, M.
A.
DePaul, A.
P.
Tran, K.
Xu, S.
M.
Dyck, K.
M.
Madalena, B.
P.
Brown, Y.
L.
Weng, S.
Li, S.
Karimi-Abdolrezaee, S.
A.
Busch, Y.
Shen, J.
Silver, Modulation of the proteoglycan receptor PTPsigma promotes recovery after spinal cord injury, Nature 518(7539) (2015) 404-8.

[3] X.
Lan, X.
Han, Q.
Li, Q.
W.
Yang, J.
Wang, Modulators of microglial activation and polarization after intracerebral haemorrhage, Nat Rev Neurol 13(7) (2017) 420-433.

[4] S.
S.
Yandamuri, T.
E.
Lane, Imaging Axonal Degeneration and Repair in Preclinical Animal Models of Multiple Sclerosis, Front Immunol 7 (2016) 189.

[5] TY Chen, SH Tai, EJ Lee, CC Huang, AC Lee, SY Huang, TS Wu, Cinnamophilin offers prolonged neuroprotection against gray and white matter damage and improves functional and electrophysiological outcomes after transient focal cerebral ischemia, Crit Care Med 39 (5) (2011) 1130-7.

[6] M.
Ueno, Y.
Nakamura, J.
Li, Z.
Gu, J.
Niehaus, M.
Maezawa, SA Crone, M.
Goulding, ML Baccei, Y.
Yoshida, Corticospinal Circuits from the Sensory and Motor Cortices Differentially Regulate Skilled Movements through Distinct Spinal Interneurons, Cell Rep 23(5) (2018) 1286-1300 e7.

End of this article