An injectable refrigerated hydrogel for Inducing local hypothermia and neuroprotection against traumatic brain injury

Abstract Hypothermia is a promising therapy for Traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI are not consistent in clinical studies due to several severe side effects. Here, an injectable refrigerated hydrogel is designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. The hydrogel has four advantages: (1) It can be injected into injured site after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) The hydrogel can biodegrade and be used for controlled drug release. (3) Released T1AM can bind to trace amine-associated receptor 1 (TAAR1) to produce cyclic adenosine monophosphate (cAMP), which induces hypothermia. (4) This hydrogel has an increased medical value due to its simple operation and ability to achieve timely treatment. This hydrogel is able to cool the brain to 30.25 ± 2.25 °C for 12 hours while maintaining the body temperature at 36.80 ± 1.75 °C after TBI. More importantly, the hypothermia induced by this hydrogel leads to the maintenance of blood-brain barrier (BBB) integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI. This cooling method can potentially be developed as a new approach for hypothermia treatment in TBI.