The impact of cigarette smoking and nicotine on traumatic brain injury: a review.

INTRODUCTION: Traumatic Brain Injury (TBI) and tobacco smoking are both serious public health problems. Many people with TBI also smoke. Nicotine, a component of tobacco smoke, has been identified as a premorbid neuroprotectant in other neurological disorders. This study aims to provide better understanding of relationships between tobacco smoking and nicotine use and effect on outcome/recovery from TBI. METHODS: PubMed database, SCOPUS, and PTSDpub were searched for relevant English-language papers. RESULTS: Twenty-nine human clinical studies and nine animal studies were included. No nicotine-replacement product use in human TBI clinical studies were identified. While smoking tobacco prior to injury can be harmful primarily due to systemic effects that can compromise brain function, animal studies suggest that nicotine as a pharmacological agent may augment recovery of cognitive deficits caused by TBI. CONCLUSIONS: While tobacco smoking before or after TBI has been associated with potential harms, many clinical studies downplay correlations for most expected domains. On the other hand, nicotine could provide potential treatment for cognitive deficits following TBI by reversing impaired signaling pathways in the brain including those involving nAChRs, TH, and dopamine. Future studies regarding the impact of cigarette smoking and vaping on patients with TBI are needed .

Potential effects of nicotine on glioblastoma and chemoradiotherapy: a review.

Introduction: Glioblastoma multiforme (GBM) has a poor prognosis despite maximal surgical resection with subsequent multi-modal radiation and chemotherapy. Use of tobacco products following diagnosis and during the period of treatment for non-neural tumors detrimentally affects treatment and prognosis. Approximately, 16-28% of patients with glioblastoma continue to smoke after diagnosis and during treatment. The literature is sparse for information-pertaining effects of smoking and nicotine on GBM treatment and prognosis. Areas covered: This review discusses cellular pathways involved in GBM progression that might be affected by nicotine, as well as how nicotine may contribute to resistance to treatment. Similarities of GBM pathways to those in non-neural tumors are investigated for potential effects by nicotine. English language papers were identified using PubMed, Medline and Scopus databases using a combination of keywords including but not limited to the following: nicotine, vaping, tobacco, e-cigarettes, smoking, vaping AND glioblastoma or brain cancer OR/AND temozolomide, carmustine, methotrexate, procarbazine, lomustine, vincristine, and neural tumor cell lines. Expert opinion: Understanding the impact of nicotine on treatment and resistance to chemotherapeutics should allow physicians to educate their patients with GBM with evidence-based recommendations about the effects of continuing to use nicotine-containing products after diagnosis and during treatment.

Do Anti-Oxidants Vitamin D3, Melatonin, and Alpha-Lipoic Acid Have Synergistic Effects with Temozolomide on Cultured Glioblastoma Cells?

Background: Cancer patients often take over-the-counter anti-oxidants as primary treatment or in combination with chemotherapy. Data about such use in glioblastoma is limited. Methods: Cultured U87-MG cells, a primary glioblastoma cell line (MU1454), U87-MG derived stem-like cells (scU87), and MU1454 derived stem-like cell lines (scMU1454) were pre-treated with one of three anti-oxidants—Vitamin D3, Melatonin, and alpha-lipoic acid (LA)—for 72 h, followed by a 72 h treatment with temozolomide (TMZ). MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assessed cell proliferation. DCFDA Cellular ROS Detection Assay and Glutathione peroxidase (GP×1) activity assessed the anti-oxidant effect of TMZ +/− an anti-oxidant drug. Results: Vitamin D3 did not affect MU1454, but had slight TMZ synergism for U87-MG. Melatonin 1 mM decreased U87-MG and MU1454 cell proliferation. As pretreatment to TMZ, melatonin 1 mM and 50 nM significantly reduced proliferation. LA 1 mM had a significant effect alone or with TMZ on U87-MG and MU1454. LA 250 uM also reduced proliferation by almost 50%. Melatonin and LA significantly enhanced the responsiveness of scMU1454 to TMZ, while Melatonin 50 nM exerted similar effects on scU87. The anti-oxidants were associated with generally decreased reactive oxygen species and limited GP×1 effects. Conclusions: Anti-oxidants may have synergistic effects with TMZ. LA offers the most promise, followed by melatonin.

Anaemia worsens early functional outcome after traumatic brain injury: a preliminary study.

OBJECTIVE: To determine early effects on outcome from traumatic brain injury (TBI) induced by controlled cortical impact (CCI) associated with anaemia in mice. HYPOTHESIS: Outcome from TBI with concomitant anaemia would be worse than TBI without anaemia. METHODS: CCI was induced with electromagnetic impaction in four groups of C57BL/6J mice: sham, sham+anaemia; TBI; and TBI+anaemia. Anaemia was created by withdrawal of 30% of calculated intravascular blood volume and saline replacement of equal volume. Functional outcome was assessed by beam-walking test and open field test (after pre-injury training) on post-injury days 3 and 7. After functional assessment, brains removed from sacrificed animals were pathological reviewed with haematoxylin and eosin, cresyl violet, Luxol Fast Blue, and IBA-1 immunostains. RESULTS: Beam-walking was similar between animals with TBI and TBI+anaemia (p = 0.9). In open field test, animals with TBI+anaemia walked less distance than TBI alone or sham animals on days 3 (p < 0.001) and 7 (p < 0.05), indicating less exploratory and locomotion behaviours. No specific pathologic differences could be identified. CONCLUSIONS: Anaemia associated with TBI from CCI is associated with worse outcome as measured by less distance travelled in the open field test at three days than if anaemia is not present.

Evidence of both von Willebrand factor deposition and factor V deposition onto AL amyloid as the cause of a severe bleeding diathesis.

: Acquired coagulopathies are common; uncommonly, adsorption of coagulation factors from the circulation into the tissues by pathologic amyloid exceeds the body's ability to produce factor and results in acquired factor deficiency. When amyloidosis does cause a coagulopathy, it is most often acquired factor X deficiency, but there are rare reports of amyloidosis being associated with other acquired factor deficiencies. We investigated a case of a severe bleeding diathesis, the cause of which was combined acquired factor V deficiency and concomitant acquired von Willebrand syndrome. Studies revealed prolonged prothrombin time and activated partial thromboplastin time. Mixing patient plasma with normal plasma corrected both the prothrombin time and activated partial thromboplastin time. Assays showed decreased factor V activity of 27%; Ristocetin cofactor activity was decreased at 49%, but von Willebrand antigen was elevated at 213%. Multimer analysis was consistent with type 2 von Willebrand syndrome. Lymph node biopsy documented amyloid light chain type (AL) amyloidosis; extraction of protein from the lymph node documented AL lambda light chain amyloid. Marrow biopsy documented IgG lambda myeloma. Immunohistochemical staining of the lymph node, using investigational polyvalent antibodies, demonstrated that both von Willebrand factor and factor V were identifiable in areas of amyloid deposition, providing evidence that these coagulation factors were adsorbed to the amyloid protein, resulting in accelerated clearance from the circulation, previously reported to be the mechanism of cases of acquired factor X deficiency in the setting of amyloidosis. Although there are case reports of acquired von Willebrand syndrome because of amyloidosis and case reports of acquired factor V deficiency because of amyloidosis, this appears to be the first reported case of concomitant acquired von Willebrand syndrome and acquired factor V deficiency because of amyloidosis, and the first report of localization of both von Willebrand protein and factor V protein to AL amyloid as a cause of a severe bleeding diathesis.