An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice

Han，Yuhan1,3; Han，Zhengzhong4; Huang，Xuyang2,5; Li，Shanshan6; Jin，Guoliang7; Feng，Junfeng3; Wu，Decheng1; Liu，Hongmei1

2024-12-01

10.1186/s12951-024-02454-z

Journal of Nanobiotechnology   影响因子和分区

1477-3155

Background: Hypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment. Methods: Pol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood–brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated. Results: This hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients. Conclusion: Our study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury. Graphical Abstract: (Figure presented.)

Hydrogel Local hypothermia Neuroprotection Traumatic brain injury

SCI

英语

第一 ; 通讯

BIOLOGY & BIOCHEMISTRY

2-s2.0-85192902972

Scopus

1.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
2.Institute of Nervous System Diseases,Xuzhou Medical University,Xuzhou,Jiangsu,221000,China
3.Brain Injury Center,Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Institute of Head Trauma,Shanghai,200127,China
4.Department of Neurosurgery,Xuzhou Children’s Hospital,Xuzhou,Jiangsu,221000,China
5.Department of Intensive Care Medicine,The Second Hospital of Jiaxing,Jiaxing,Zhejiang,314000,China
6.Department of Forensic Medicine,Xuzhou Medical University,Xuzhou,Jiangsu,221000,China
7.Department of Neurology,Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221000,China

Han，Yuhan,Han，Zhengzhong,Huang，Xuyang,et al. An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice[J]. Journal of Nanobiotechnology,2024,22(1).

Han，Yuhan.,Han，Zhengzhong.,Huang，Xuyang.,Li，Shanshan.,Jin，Guoliang.,...&Liu，Hongmei.(2024).An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice.Journal of Nanobiotechnology,22(1).

Han，Yuhan,et al."An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice".Journal of Nanobiotechnology 22.1(2024).