Effect of Gender on Recovery After Spinal Cord Injury

Chan, Wai Man; Mohammed, Yahya Abdel Aziz; Lee, Isabel; Pearse, Damien D.

doi:10.1007/s12975-012-0249-7

Cited by 48 publications

(23 citation statements)

References 68 publications

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“…In contrast to estrogens and progesterone, how androgens mediate sex-dependent effects in SCI is less studied. Whether testosterone exhibits an overall neuroprotective or detrimental effect on recovery from SCI remains controversial (43,102). Current evidence supporting testosterone as potentially neurotoxic comes from the observation that castration of male rodents pre-SCI improves locomotor recovery, an effect that was further abrogated following exogenous delivery of dihydrotestosterone (16).…”

Section: Testosterone Mediates Sex Dependent Effects On Sci Recoverymentioning

confidence: 99%

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

et al. 2020

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In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies.

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Section: Testosterone Mediates Sex Dependent Effects On Sci Recoverymentioning

confidence: 99%

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

et al. 2020

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“…52 Additionally, much experimental and clinical evidence suggests that females recover better after SCI, as several experimental results suggest a gender bias in outcome that favors females. 53 These observations indicate a strong gender effect in SCI outcomes. Yet, sex-differences in recovery from SCI are not estrogen-dependent, as shown by an experiment in which estradiol (E2) did not provide a viable therapy following SCI.…”

Section: Discussionmentioning

confidence: 95%

Myristoylated alanine‐rich C‐kinase substrate effector domain peptide improves sex‐specific recovery and axonal regrowth after spinal cord injury

et al. 2020

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Myristoylated alanine‐rich C‐kinase substrate (MARCKS) is an intracellular receptor for polysialic acid. MARCKS supports development, synaptic plasticity, and regeneration after injury. MARCKS binds with its functionally essential effector domain (ED) to polysialic acid. A 25‐mer peptide comprising the ED of MARCKS stimulates neuritogenesis of primary hippocampal neurons after addition to the culture. This motivated us to investigate whether ED peptide has similar effects in spinal cord injury. ED peptide supported recovery and regrowth of monoaminergic axons in female, but not in male mice. Sex‐specific differences in response to ED peptide application also occurred in cultured neurons. In female but not male neurons, the ED peptide enhanced neurite outgrowth that could be suppressed by inhibitors of the estrogen receptors α and β, fibroblast growth factor receptor‐1, protein kinase C, and matrix metalloproteinase 2. In addition, we observed female‐specific elevation of phosphorylated MARCKS levels after ED peptide treatment. In male neurons, the ED peptide enhanced neuritogenesis in the presence of an androgen receptor inhibitor to the extent seen in ED peptide‐treated female neurons. However, inhibition of androgen receptor did not lead to increased phosphorylation of MARCKS. These results provide insights into the functions of a novel compound contributing to gender‐dependent regeneration.

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“…Gender-related influences on the outcome after SCI have been reported with a better recovery in females. The improved recovery has, at least partly, been attributed to the regulation of the SCI-induced neuroinflammatory response by sex hormones [ 43 , 44 ]. In our cohort, analyzing the validated antibody responses based on gender did not show any sex-related differences in antibody reactivity against the novel identified targets.…”

Section: Discussionmentioning

confidence: 99%

Antibody profiling identifies novel antigenic targets in spinal cord injury patients

Palmers

Ydens

Put

et al. 2016

J Neuroinflammation

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BackgroundRecent evidence implicates antibody responses as pivotal damaging factors in spinal cord injury (SCI)-induced neuroinflammation. To date, only a limited number of the antibody targets have been uncovered, and the discovery of novel targets with pathologic and clinical relevance still represents a major challenge.MethodsIn this study, we, therefore, applied an unbiased, innovative and powerful strategy, called serological antigen selection (SAS), to fully identify the complex information present within the antibody repertoire of SCI patients.ResultsWe constructed a high-quality cDNA phage display library derived from human spinal cord tissue to screen for antibody reactivity in pooled plasma samples from traumatic SCI patients (n = 10, identification cohort). By performing SAS, we identified a panel of 19 antigenic targets to which the individual samples of the plasma pool showed antibody reactivity. Sequence analysis to identify the selected antigenic targets uncovered 5 known proteins, to which antibody reactivity has not been associated with SCI before, as well as linear peptides. Immunoreactivity against 9 of the 19 novel identified targets was validated in 41 additional SCI patients and an equal number of age- and gender-matched healthy subjects. Overall, we found elevated antibody levels to at least 1 of the 9 targets in 51 % of our total SCI patient cohort (n = 51) with a specificity of 73 %. By combining 6 of these 9 targets into a panel, an overall reactivity of approximately half of the SCI patients could be maintained while increasing the specificity to 82 %.ConclusionsIn conclusion, our innovative high-throughput approach resulted in the identification of previously unexplored antigenic targets with elevated immunoreactivity in more than 50 % of the SCI patients. Characterization of the validated antibody responses and their targets will not only provide new insight into the underlying disease processes of SCI pathology but also significantly contribute to uncovering potential antibody biomarkers for SCI patients.

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Effect of Gender on Recovery After Spinal Cord Injury

Cited by 48 publications

References 68 publications

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

Myristoylated alanine‐rich C‐kinase substrate effector domain peptide improves sex‐specific recovery and axonal regrowth after spinal cord injury

Antibody profiling identifies novel antigenic targets in spinal cord injury patients

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