Search

Traumatic brain injury (TBI) is a significant global health issue due to its high morbidity and mortality, as well as its adverse outcomes. The resulting excessive healthcare and economic burden make it urgent to find effective drugs for TBI. Aminophylline (AMP), a classical drug widely used in the treatment of cardiovascular diseases and bronchiectasis, has recently been found to play an important role in protecting neurons in hypoxia brain injury by a variety of mechanisms. However, its therapeutic effect on TBI remains unknown. To this end, the present study aims to explore whether and how AMP improves TBI prognosis, as well as the underlying mechanisms. We found that AMP administration ameliorated neuronal ferroptosis in the cortex, improved cognitive impairment and motor dysfunction in mice following controlled cortical impact (CCI). microRNA (miRNA) profiling and related validation experiments revealed that miR-128-3p expression significantly decreased at 3h and 6h after CCI, and this change was further enhanced after AMP administration. Subsequent gain of function studies demonstrated that over-expressing miR-128-3p can aggravate neuronal ferroptosis by targeting recombinant solute carrier family 7, member 11 (Slc7a11), through which AMP exerted its therapeutic role in attenuating the cognitive impairment and motor dysfunction in mice following CCI. Overall, this study reports for the first time that AMP protects against ferroptotic neuronal death in CCI mice through miR-128-3p / Slc7a11 axis, which could be a potential treatment for TBI patients.

Background: A significant part of blast injury is accompanied by hemorrhagic shock (BS), while research on its fluid resuscitation strategies have not been reported. Although blood products are usually recommended in most resuscitation cases, they are less available in certain conditions. To this end, here, we focused on a widely used and more accessible fluid type- crystalloid fluid, in BS treatment. Methods: We conducted studies in rats comparing the therapeutic effects of 3 different crystalloid solutions at different time points after BS, and explored the underlying mechanisms. Generally, the survival rates gradually dropped along with the time when fluid resuscitation was given. Results: Among different types of solution, the hypertonic saline (HS) group showed th objective: A significant part of blast injury is accompanied by hemorrhagic shock (BS), while researches on its fluid resuscitation strategies have not been reported. Although blood products are usually recommended in most resuscitation cases, they are less available in certain conditions. To this end, here we focused on a widely used and more accessible fluid type- crystalloid fluid, in BS treatment. Results: Among different types of solution, the hypertonic saline (HS) group showed the highest survival rates. The lactated Ringer’s solution (LR) only displayed lifesaving effect at 0.5h resuscitation time point. Moreover, it is worth noting that the survival rates of the normal saline (NS) group at all the time points were lower than the non-treatment control. Mechanism study in rats indicated that the therapeutic differences may be caused by varied degrees of pulmonary edema and inflammatory responses under different crystalloid fluid resuscitation. Conclusions: In conclusion, we assessed the effects and investigated the mechanisms of different crystalloid fluid resuscitation strategies for BS for the first time, which potentially contributes to the establishment of guidance for crystalloid fluid resuscitation of BS patients.

Explosive blast-related traumatic brain injuries (bTBI) are common in war zones and urban terrorist attacks. These bTBIs often result in complex neuropathologic damage and neurologic complications. However, there is still a lack of specific strategies for diagnosing and/or treating bTBIs. The sub-ventricular zone (SVZ), which undergoes adult neurogenesis, is critical for the neurological maintenance and repair after brain injury. However, the cellular responses and mechanisms that trigger and modulate these activities in the pathophysiological processes following bTBI remain poorly understood. Here we employ single-nucleus RNA-sequencing (snRNA-seq) of the SVZ from mice subjected to a bTBI. This data-set, including 15272 cells (7778 bTBI and 7494 control) representing all SVZ cell types and is ideally suited for exploring the mechanisms underlying the pathogenesis of bTBIs. Additionally, it can serve as a reference for future studies regarding the diagnosis and treatment of bTBIs.

Next-generation sequencing and single-cell RNA sequencing (scRNA-seq) technologies have advanced rapidly in recent years. scRNA-seq reveals the unique gene expression of each cell type, providing directions for exploring cell heterogeneity, cell type-specific responses to injury/disease, and the mechanisms underlying these processes. The development of sequencing technology and improved sequencing throughput have brought about a revolution in single-cell transcriptome study, bringing great benefits to the fields of medicine and biomedical science. From our perspective, certain issues in forensic medicine may potentially be addressed using single-cell transcriptome studies; however, this powerful technique has not yet attracted sufficient attention in forensic medicine-associated research. Therefore, examining and reviewing the latest developments and applications of single-cell transcriptome studies, we present our views on the future directions of forensic research using this technology, aiming to expand the frontiers of forensic science.

Interventions for preventing cognitive dysfunction after traumatic brain injury (TBI) are limited. Given that adult hippocampal neurogenesis after brain injury contributes to cognitive recovery, and hippocampal neurogenesis is potentially affected by nutritional factors, the aim of this study was to examine whether fasting could promote hippocampal neurogenesis and thus ameliorate the cognitive defects after TBI.The present study used 8- to 10-wk-old C57 BL/6 N mice weighing 23 g, half males and half females. The mice were randomly assigned to each group, with 10 to 18 mice per group. All mice were housed in an approved animal facility with a 12-h light/dark cycle. In the metabolic study (food intake, body weight, blood glucose, triacylglycerol, total cholesterol, and β-hydroxybutyric acid ), 54 mice (male:female = 1:1) were randomized to the ad libitum (AL) group (n = 18) and the intermittent fasting (IF) group (n = 36). In the neurogenesis study, 45 mice (male:female = 1:1) were randomized to AL (n = 18), IF (n = 9), IF + scramble (n = 9), and the IF + neuropeptide Y (NPY)_siRNA (n = 9) groups. In the Morris water maze test, 48 mice (male:female = 1:1) were randomized to AL (n = 12), IF (n = 12), IF + scramble (n = 12), and the IF + NPY_siRNA (n = 12) groups.We showed that a 1-mo-long IF regimen enhanced the proliferation of neural stem cells in the subgranular zone of the hippocampus 3 d after TBI, in addition to improving the cognitive performance in the Morris water maze test. Furthermore, an increase in the hippocampal NPY expression was detected in the IF group after the injury, compared with the mice fed AL, and local knockdown of NPY in vivo attenuated the effects of IF on TBI.These findings suggest that IF promotes hippocampal neurogenesis after TBI by a mechanism that involves enhancement of NPY expression, to alleviate cognitive dysfunction caused by injury.

Interventions for preventing cognitive dysfunction post traumatic brain injury (TBI) is limited. Given that adult hippocampal neurogenesis (AHN) after brain injury contributes to cognitive recovery, and that the AHN is potentially affected by nutritional factors, we asked whether fasting could promote AHN and thus ameliorates cognitive defects after TBI. Here we show that a one-month intermittent fasting (IF) regimen enhanced proliferation of neural stem cells (NSCs) in the subgranular zone (SGZ) of hippocampus 3 days post TBI, as well as improved cognitive performance in Morris water maze (MWM) test. Furthermore, an increase in hippocampal Npy expression was detected in IF group after injury, compared to the mice fed ad libitum (AL), and locally knock-down of Npy in vivo attenuated the aforementioned effects of IF in TBI. These findings suggest that IF promotes AHN following TBI by a mechanism involving enhancement of Npy expression, which may offer novel interventions that might prevent cognitive dysfunction caused by injury.

It has widely been accepted that food restriction (FR) without malnutrition has multiple health benefits. Various calorie restriction (CR) and intermittent fasting (IF) regimens have recently been reported to exert neuroprotective effects in traumatic brain injury (TBI) through variable mechanisms. However, the evidence connecting CR or IF to neuroprotection in TBI as well as current issues remaining in this research field have yet to be reviewed in literature. The objective of our review was therefore to weigh the evidence that suggests the connection between CR/IF with recovery promotion following TBI. Medline, Google Scholar and Web of Science were searched from inception to 25 February 2022. An overwhelming number of results generated suggest that several types of CR/IF play a promising role in promoting post-TBI recovery. This recovery is believed to be achieved by alleviating mitochondrial dysfunction, promoting hippocampal neurogenesis, inhibiting glial cell responses, shaping neural cell plasticity, as well as targeting apoptosis and autophagy. Further, we represent our views on the current issues and provide thoughts on the future direction of this research field.

Optogenetics is emerging as an ideal method for controlling cellular activity. It overcomes some notable shortcomings of conventional methods in the elucidation of neural circuits, promotion of neuroregeneration, prevention of cell death and treatment of neurological disorders, although it is not without its own limitations. In this review, we narratively review the latest research on the improvement and existing challenges of optogenetics, with a particular focus on the field of brain injury, aiming at advancing optogenetics in the study of brain injury and collating the issues that remain. Finally, we review the most current examples of research, applying photostimulation in clinical treatment, and we explore the future prospects of these technologies.