The National Football League (NFL) has seen increasing scrutiny regarding its management of concussions, especially following an on-field incident involving the Miami Dolphins' quarterback Tua ...Tagovailoa in the 2022 season. We hope to elucidate the recent trends in the diagnosis and management of concussions during the course of 5 NFL seasons from 2019 to 2023.
We queried the NFL injury reports from the 2019 through 2023 database recording players listed with concussions. The weeks missed were calculated using the NFL game logs. Players' concussions that did not occur in the games, those complicated by other injuries, and those affected by roster status were excluded.
Searches of the NFL injury reports resulted in the identification of 664 of 692 concussions (96%) that occurred in regular season games across the 2019-2023 seasons. During the course of these 5 seasons, 31% of the players returned without missing a game, 39% of the players missed 1 game, and 30% of the players missed ≥2 games. No significant difference in the number of concussions per game or weeks missed was observed across the seasons observed. Players with concussions on teams that made the playoffs saw fewer weeks missed than those on non-playoff teams (0.86 vs. 1.37; P = 0.002).
Since the start of the 2021 NFL season, an increasing incidence of concussions has been noted; however, there was no change observed in the number of weeks missed after the concussions. Trends in the rates of concussions across the seasons remain largely stable, despite increased scrutiny over concussions in the sport.
Microglia are the main immune cells of the brain and contribute to common brain diseases. However, it is unclear how microglia influence neuronal activity and survival in the injured brain in vivo. ...Here we develop a precisely controlled model of brain injury induced by cerebral ischaemia combined with fast in vivo two-photon calcium imaging and selective microglial manipulation. We show that selective elimination of microglia leads to a striking, 60% increase in infarct size, which is reversed by microglial repopulation. Microglia-mediated protection includes reduction of excitotoxic injury, since an absence of microglia leads to dysregulated neuronal calcium responses, calcium overload and increased neuronal death. Furthermore, the incidence of spreading depolarization (SD) is markedly reduced in the absence of microglia. Thus, microglia are involved in changes in neuronal network activity and SD after brain injury in vivo that could have important implications for common brain diseases.
The modified Brain Injury Guidelines (mBIG) provide a framework to stratify traumatic brain injury (TBI) patients based on clinical and radiographic factors in level 1 and 2 trauma centers. ...Approximately 75% of all U.S. hospitals do not carry any trauma designation yet could also benefit from these guidelines. To the best of our knowledge, this is the first report of applying the mBIG protocol in a community hospital without any trauma designation.
All adult patients with a TBI in a single center from 2020 to 2022 were retrospectively classified into mBIG categories. The primary outcomes included neurological deterioration, progression on computed tomography of the head, and surgical intervention. Additional outcomes included the hospital costs incurred by the mBIG 1 and mBIG 2 groups.
Of the 116 included patients, 35 (30%) would have stratified into mBIG 1, 23 (20%) into mBIG 2, and 58 (50%) into mBIG 3. No patient in mBIG 1 had a decline in neurological examination findings or progression on computed tomography of the head or required neurosurgical intervention. Three patients in mBIG 2 had radiographic progression and one required surgical decompression. Two patients in mBIG 3 demonstrated a neurological decline and six had radiographic progression. Of the 21 patients who received surgical intervention, 20 were stratified into mBIG 3. Implementation of the mBIG protocol could have reduced costs by >$250,000 during the 2-year period.
The mBIG protocol can safely stratify patients in a nontrauma hospital. Because nontrauma centers tend to see more patients with minor TBIs, implementation could result in significant cost savings, reduce unnecessary hospital and intensive care unit resources, and reduce transfers to a tertiary institution.
There is a great clinical need to identify the underlying mechanisms, as well as related biomarkers, and treatment targets, for traumatic brain injury (TBI). Neuroinflammation is a central ...pathophysiological feature of TBI. NLRP3 inflammasome activity is a necessary component of the innate immune response to tissue damage, and dysregulated inflammasome activity has been implicated in a number of neurological conditions. This paper introduces the NLRP3 inflammasome and its implication in the pathogenesis of neuroinflammatory-related conditions, with a particular focus on TBI. Although its role in TBI has only recently been identified, findings suggest that priming and activation of the NLRP3 inflammasome are upregulated following TBI. Moreover, recent studies utilizing specific NLRP3 inhibitors have provided further evidence that this inflammasome is a major driver of neuroinflammation and neurobehavioral disturbances following TBI. In addition, there is emerging evidence that circulating inflammasome-associated proteins may have utility as diagnostic biomarkers of neuroinflammatory conditions, including TBI. Finally, novel and promising areas of research will be highlighted, including the potential involvement of the NLRP3 inflammasome in mild TBI, how factors such as biological sex may affect NLRP3 activity in TBI, and the use of emerging biomarker platforms. Taken together, this review highlights the exciting potential of the NLRP3 inflammasome as a target for treatments and biomarkers that may ultimately be used to improve TBI management.
Traumatic brain injuries (TBI) trigger an inflammatory cascade that causes edema and inflammation through infiltration by peripheral immune cells and activation of brain resident microglia. There are ...currently no therapies that effectively control neuroinflammation to ameliorate neurological outcomes. Our group has tested autologous bone-marrow mononuclear cells (BM-MNC) as a therapy for TBI in both adult and pediatric cases and found that BM-MNC dampened the innate immune response to injury and contributed to white matter preservation. There are many ways in which infused BM-MNC may modulate neuroinflammation. We hypothesize that indoleamine2,3-dioxygenase (IDO), an enzyme that initiates tryptophan catabolism into N-formyl-kynurenine and is upregulated in response to inflammation, plays a key role in immunoregulation. IDO can modulate T cell behavior and reduce inflammation through tryptophan and kynurenine levels, decreasing T cell activation and activating regulatory T cells.
In an effort to predict MNC therapy outcomes, and establish a feasible assay that can act as a novel release criterion for these cell products, we sought to identify, characterize, and quantify IDO expressing subsets by flow cytometry and correlate it to supernatant levels and mRNA expression. In parallel, we assessed correlations within our existing MNC therapy for TBI data, specifically analyzing the relationships between the composition of infused product, serum cytokines, and imaging outcomes. Since MNC from multiple sources are currently being investigated to treat a number of indications in clinical trials, we tested MNCs derived from bone marrow, umbilical cord, and peripheral blood using a broad blood cytometric panel as well as more targeted myeloid and lymphoid panels.
We found that IDO mRNA and protein are upregulated upon inflammatory stimulation in vitro and that IDO-expressing cells are CD14+CD11c+ (Figure 1). The frequency of IDO and the frequency of monocytes was increased upon stimulation in bone marrow and umbilical cord blood samples but not in peripheral blood samples (Figure 2). After 24-hour stimulation, CD14+ cells were able to suppress allogeneic T cell proliferation. Interestingly, we have found that the frequency of monocytes in infused product was strongly correlated to better neurological outcomes in our pediatric TBI clinical trial.
Our current investigation suggests that monocyte frequency may be an indicator of efficacy for BM-MNC to treat TBI using IDO.
While numerous studies have suggested the involvement of cerebrovascular dysfunction in the pathobiology of blast‐induced traumatic brain injury (bTBI), its exact mechanisms and how they affect the ...outcome of bTBI are not fully understood. Our previous study showed the occurrence of cortical spreading depolarization (CSD) and subsequent long‐lasting oligemia/hypoxemia in the rat brain exposed to a laser‐induced shock wave (LISW). We hypothesized that this hemodynamic abnormality is associated with shock wave‐induced generation of nitric oxide (NO). In this study, to verify this hypothesis, we used an NO‐sensitive fluorescence probe, diaminofluorescein‐2 diacetate (DAF‐2 DA), for real‐time in vivo imaging of male Sprague–Dawley rats' brain exposed to a mild‐impulse LISW. We observed the most intense fluorescence, indicative of NO production, along the pial arteriolar walls during the period of 10–30 min post‐exposure, parallel with CSD occurrence. This post‐exposure period also coincided with the early phase of hemodynamic abnormalities. While the changes in arteriolar wall fluorescence measured in rats receiving pharmacological NO synthase inhibition by nitro‐L‐arginine methyl ester (L‐NAME) 24 h before exposure showed a temporal profile similar to that of changes observed in LISW‐exposed rats with CSD, their intensity level was considerably lower; this suggests partial involvement of NOS in shock wave‐induced NO production. To the best of our knowledge, this is the first real‐time in vivo imaging of NO in rat brain, confirming the involvement of NO in shock‐wave‐induced hemodynamic impairments. Finally, we have outlined the limitations of this study and our future research directions.
We hypothesized that NO generation was associated with hemodynamic dysfunction in the brain exposed to a shock wave. Our in vivo imaging using NO‐sensitive fluorescence probe showed significantly increased NO fluorescence mainly along the pial arterioles in the rat brain exposed to a laser‐induced shock wave, supporting the hypothesis.
Traumatic brain injury (TBI) and spinal cord injury (SCI) are pathological events that lead to neuropathological conditions which have in consequence the initiation of pro‐inflammatory cytokine ...production. Neuroinflammation plays a key role in the secondary phase of both TBI and SCI after initial cell death. Activation of cytoplasmic inflammasome complexes is regarded as the essential step of neuroinflammation and a key trigger for neuronal death called pyroptosis. Inflammasome complexes are involved in activation of caspase‐1 which catalyzes the cleavage of pro‐interleukins into their active forms (including interleukin‐18 IL‐18 and IL‐1β). The focus of this article is to discuss the time‐course and regulation of inflammasome assembly and activation during TBI and SCI and their targeting in designing therapeutic approaches. We particularly focus on the inflammasomes NLRP1 and NLRP3 which play a pivotal function during TBI and SCI in the central nervous system (CNS).
Neuroinflammation plays a key role in the secondary phase of both TBI and SCI after initial cell death. Activation of cytoplasmic inflammasome complexes is regarded as the essential step of neuroinflammation and a key trigger for neuronal death called pyroptosis. The NLRP1 and NLRP3 inflammasome complexs are possibly the dominant types of inflammasomes activated in the TBI and SCI.
•Vasospasm contributes to delayed ischemic neurologic deficits and is associated with aneurysmal subarachnoid hemorrhage.•Traumatic brain injury is the leading cause of subarachnoid ...hemorrhage.•Traumatic subarachnoid hemorrhage and vasospasm are easily detected with CT angiogram of the head.•Traumatic subarachnoid hemorrhage may result in traumatic brain injury from vasospasm and delayed cerebral ischemia.
To determine the incidence of vasospasm in traumatic brain injury patients with traumatic subarachnoid hemorrhage.
IRB approval was obtained for this retrospective chart review. An institutional trauma database was queried for adult patients with traumatic brain injury (TBI) and traumatic subarachnoid hemorrhage (tSAH) seen on CT head obtained within 20 days. The presence of vasospasm on CTA was determined by radiology report. Association between categorical background characteristics and intracranial vasospasm was assessed by the chi-square test and association between a continuous variables and intracranial vasospasm was assessed by a paired t-test.
1142 patients with traumatic SAH were identified from the trauma database. 792 patients were excluded: 142 for age <18, 632 did not have CT angiography, and 18 had non-traumatic SAH. 350 patients were analyzed, of which 28 (8 %) had vasospasm. Traumatic vasospasm was associated with higher-grade TBI based on Cochran-Armitage trend test (p < 0.05). Vasospasm patients had longer length of stay in the ICU (mean days 13.64 vs 7.24, P < 0.001), and had a higher incidence of death (39.29 % vs 20.81 %), although this did not reach statistical significance.
Intracranial vasospasm, specifically in patients with tSAH, is associated with more severe TBI and longer stays in the ICU. Our incidence is smaller compared to other studies likely due to the retrospective nature and the infrequency of obtaining CT angiography after initial presentation. Prospective studies are warranted as the incidence is significant and may represent a point of intervention for TBI.
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