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Distinguishing the Unique Neuropathological Profile of Blast Polytrauma

View Article: PubMed Central - PubMed

ABSTRACT

Traumatic brain injury sustained after blast exposure (blast-induced TBI) has recently been documented as a growing issue for military personnel. Incidence of injury to organs such as the lungs has decreased, though current epidemiology still causes a great public health burden. In addition, unprotected civilians sustain primary blast lung injury (PBLI) at alarming rates. Often, mild-to-moderate cases of PBLI are survivable with medical intervention, which creates a growing population of survivors of blast-induced polytrauma (BPT) with symptoms from blast-induced mild TBI (mTBI). Currently, there is a lack of preclinical models simulating BPT, which is crucial to identifying unique injury mechanisms of BPT and its management. To meet this need, our group characterized a rodent model of BPT and compared results to a blast-induced mTBI model. Open field (OF) performance trials were performed on rodents at 7 days after injury. Immunohistochemistry was performed to evaluate cellular outcome at day seven following BPT. Levels of reactive astrocytes (GFAP), apoptosis (cleaved caspase-3 expression), and vascular damage (SMI-71) were significantly elevated in BPT compared to blast-induced mTBI. Downstream markers of hypoxia (HIF-1α and VEGF) were higher only after BPT. This study highlights the need for unique therapeutics and prehospital management when handling BPT.

No MeSH data available.


Representative images show HIF-1α expression is elevated in the BPT group (∗p < 0.05) when compared to the sham group. (Top right) HIF-1α was colocalized with DAPI around the vessels in the BPT group.
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fig6: Representative images show HIF-1α expression is elevated in the BPT group (∗p < 0.05) when compared to the sham group. (Top right) HIF-1α was colocalized with DAPI around the vessels in the BPT group.

Mentions: HIF-1α is a transcription factor that is involved in several injury modalities where hypoxia occurs, including TBI [25]. HIFs are heterodimeric transcription factors composed of an oxygen-sensitive α-subunit and a constitutively expressed β-subunit. Under normoxia, the HIF-1α subunit is constitutively transcribed but constantly targeted for degradation. As oxygen tension drops, the degradation enzymes are inhibited, which results in cytoplasmic stabilization of the α-subunits. For the BPT group, HIF-1α expression was increased in the amygdala at seven days after blast compared to the sham group (Figure 6). In Figure 6, HIF-1α appears to be colocalized with DAPI around major vessels, showing that hypoxia is potentially being sensed first due to low blood oxygen concentration and this could be an ongoing mechanism.


Distinguishing the Unique Neuropathological Profile of Blast Polytrauma
Representative images show HIF-1α expression is elevated in the BPT group (∗p < 0.05) when compared to the sham group. (Top right) HIF-1α was colocalized with DAPI around the vessels in the BPT group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382305&req=5

fig6: Representative images show HIF-1α expression is elevated in the BPT group (∗p < 0.05) when compared to the sham group. (Top right) HIF-1α was colocalized with DAPI around the vessels in the BPT group.
Mentions: HIF-1α is a transcription factor that is involved in several injury modalities where hypoxia occurs, including TBI [25]. HIFs are heterodimeric transcription factors composed of an oxygen-sensitive α-subunit and a constitutively expressed β-subunit. Under normoxia, the HIF-1α subunit is constitutively transcribed but constantly targeted for degradation. As oxygen tension drops, the degradation enzymes are inhibited, which results in cytoplasmic stabilization of the α-subunits. For the BPT group, HIF-1α expression was increased in the amygdala at seven days after blast compared to the sham group (Figure 6). In Figure 6, HIF-1α appears to be colocalized with DAPI around major vessels, showing that hypoxia is potentially being sensed first due to low blood oxygen concentration and this could be an ongoing mechanism.

View Article: PubMed Central - PubMed

ABSTRACT

Traumatic brain injury sustained after blast exposure (blast-induced TBI) has recently been documented as a growing issue for military personnel. Incidence of injury to organs such as the lungs has decreased, though current epidemiology still causes a great public health burden. In addition, unprotected civilians sustain primary blast lung injury (PBLI) at alarming rates. Often, mild-to-moderate cases of PBLI are survivable with medical intervention, which creates a growing population of survivors of blast-induced polytrauma (BPT) with symptoms from blast-induced mild TBI (mTBI). Currently, there is a lack of preclinical models simulating BPT, which is crucial to identifying unique injury mechanisms of BPT and its management. To meet this need, our group characterized a rodent model of BPT and compared results to a blast-induced mTBI model. Open field (OF) performance trials were performed on rodents at 7 days after injury. Immunohistochemistry was performed to evaluate cellular outcome at day seven following BPT. Levels of reactive astrocytes (GFAP), apoptosis (cleaved caspase-3 expression), and vascular damage (SMI-71) were significantly elevated in BPT compared to blast-induced mTBI. Downstream markers of hypoxia (HIF-1&alpha; and VEGF) were higher only after BPT. This study highlights the need for unique therapeutics and prehospital management when handling BPT.

No MeSH data available.