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Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood–brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients.

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This study has been presented as an e-poster in XXIII SENEC Congress on 2019 at Salamanca, Spain.

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SARS-CoV2 infection can lead to a prothrombotic state. Large vessel occlusion, as well as malignant cerebral stroke have been described in COVID-19 patients. In the following months, given the increase in COVID-19 cases, an increase in malignant cerebral SARS-CoV2 associated strokes are expected. The baseline situation of the patients as well as the risk of evolution to a serious disease due to the virus, depict a unique scenario. Decompressive craniectomy is a life-saving procedure indicated in patients who suffer a malignant cerebral stroke; however, it is unclear whether the same eligibility criteria should be used for patients with COVID-19. To our knowledge seven cases of decompressive craniectomy and malignant cerebral stroke have been described to date. We report on a 39-year-old female with no major risk factors for cerebrovascular disease, apart from oral contraception, and mild COVID-19 symptoms who suffered from left hemispheric syndrome. The patient underwent endovascular treatment with stenting and afterward decompressive craniectomy due to a worsening neurological status with unilateral unreactive mydriasis. We present the case and provide a comprehensive review of the available literature related to the surgical treatment for COVID-19 associated malignant strokes, to establish whether the same eligibility criteria for non-COVID-19 associated strokes should be used. Eight patients, including our case, were surgically managed due to malignant cerebral stroke. Seven of these patients received decompressive craniectomy, and six of them met the eligibility criteria of the current stroke guidelines. The mortality rate was 33%, similar to that described in non-COVID-19 cases. Two patients had a left middle cerebral artery (MCA) and both survived after decompressive craniectomy. Our results support that decompressive craniectomy, using the current stroke guidelines, should be considered an effective life-saving treatment for COVID-19-related malignant cerebral strokes.

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