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Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model
Mang Xiao1, Xianghong Li1, Li Wang1,2
1Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA.
International Journal of Molecular Sciences
|July 14, 2023
Summary
Radiation combined with skin injury (RCI) causes more severe outcomes than radiation injury (RI) alone, including increased mortality and delayed wound healing. Both RCI and RI induce brain inflammation and neural cell damage.
Area of Science:
- Neuroscience
- Radiation Biology
- Immunology
Background:
- Radiation exposure can cause significant systemic and neurological damage.
- The combined effects of radiation and concurrent injuries, such as skin wounds, on brain health are not fully understood.
Purpose of the Study:
- To investigate the impact of total-body gamma irradiation (RI) and combined radiation with skin puncture wound (RCI) on inflammatory responses and neural cell integrity in the mouse brain.
- To compare the severity of brain injury induced by RI versus RCI.
Main Methods:
- Mice were subjected to sham procedure, skin wound (SW), RI, or RCI.
- Survival, body weight, and wound healing were monitored.
- Brain tissue and serum were analyzed on day 30 using Western blot, immunohistochemistry, and chemokine analysis.
- Neurogenesis markers (DCX) and neural cell markers (E-cadherin, MASH1, NeuroD1, NeuN) were assessed.
Main Results:
- RCI led to higher mortality and body weight loss than RI, and significantly delayed skin wound healing compared to SW.
- Both RI and RCI increased brain chemokines (Eotaxin, IP-10, MIG, 6Ckine/Exodus2, MCP-5, TIMP-1) and upregulated IP-10 and p21.
- RI and RCI activated astrocytes and endothelial cells, increased blood-brain barrier (BBB) leakage (ICAM1, GFAP), and downregulated neurogenesis (DCX).
- Expression of neural stem cell, progenitor, and mature neuron markers (E-cadherin, MASH1, NeuroD1, NeuN) was decreased, indicating widespread neural cell damage.
- RCI exacerbated neural cell damage more than RI.
Conclusions:
- Radiation injury and combined radiation with skin injury induce significant brain inflammation and damage through inflammatory pathways.
- Combined radiation and skin injury (RCI) results in more severe systemic effects and exacerbates neural cell damage compared to radiation injury (RI) alone.
- The study highlights the detrimental impact of combined injuries on brain health and neurogenesis.
