Combination therapies

Oudega, Martin; Bradbury, Elizabeth J.; Ramer, Matt S.

doi:10.1016/b978-0-444-52137-8.00038-3

Cited by 22 publications

(19 citation statements)

References 242 publications

(283 reference statements)

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“…In addition, better understanding cell-cell interactions using in vitro (co-culture, media transfer) and in vivo strategies would further aid development of combinatorial strategies [164,262]. Although combining treatments presents challenges (e.g., number of groups, treatment compatibility/safety, optimal timing) [340], revealing new effective treatments and thoughtfully combining complementary strategies could lead to robust improvements and novel therapies.…”

Section: Future Directions: Manipulating Glial Responses To Improve Nmentioning

confidence: 99%

Glial Cells Shape Pathology and Repair After Spinal Cord Injury

2018

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Glial cell types were classified less than 100 years ago by del Rio-Hortega. For instance, he correctly surmised that microglia in pathologic central nervous system (CNS) were "voracious monsters" that helped clean the tissue. Although these historical predictions were remarkably accurate, innovative technologies have revealed novel molecular, cellular, and dynamic physiologic aspects of CNS glia. In this review, we integrate recent findings regarding the roles of glia and glial interactions in healthy and injured spinal cord. The three major glial cell types are considered in healthy CNS and after spinal cord injury (SCI). Astrocytes, which in the healthy CNS regulate neurotransmitter and neurovascular dynamics, respond to SCI by becoming reactive and forming a glial scar that limits pathology and plasticity. Microglia, which in the healthy CNS scan for infection/damage, respond to SCI by promoting axon growth and remyelination-but also with hyperactivation and cytotoxic effects. Oligodendrocytes and their precursors, which in healthy tissue speed axon conduction and support axonal function, respond to SCI by differentiating and producing myelin, but are susceptible to death. Thus, post-SCI responses of each glial cell can simultaneously stimulate and stifle repair. Interestingly, potential therapies could also target interactions between these cells. Astrocyte-microglia cross-talk creates a feed-forward loop, so shifting the response of either cell could amplify repair. Astrocytes, microglia, and oligodendrocytes/precursors also influence post-SCI cell survival, differentiation, and remyelination, as well as axon sparing. Therefore, optimizing post-SCI responses of glial cells-and interactions between these CNS cells-could benefit neuroprotection, axon plasticity, and functional recovery.

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Section: Future Directions: Manipulating Glial Responses To Improve Nmentioning

confidence: 99%

Glial Cells Shape Pathology and Repair After Spinal Cord Injury

2018

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“…The main problem with SCI is that a cascade of independent events are initiated after the trauma; therefore, a combination therapy is required to better approach the progressive stages of this illness (Oudega et al, 2012). The devastating effects of SCI are associated with its immediate and secondary effects that result in cell degeneration at the trauma site and surrounding areas.…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: Their antioxidant effect and role of estrogen receptor alpha

et al. 2014

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17β-Estradiol is a multi-active steroid that imparts neuroprotection via diverse mechanisms of action. However, its role as a neuroprotective agent after spinal cord injury (SCI), or the involvement of the estrogen receptor-alpha (ER-α) in locomotor recovery, is still a subject of much debate. In this study, we evaluated the effects of estradiol and of Tamoxifen (an estrogen receptor mixed agonist/antagonist) on locomotor recovery following SCI. To control estradiol cyclical variability, ovariectomized female rats received empty or estradiol filled implants, prior to a moderate contusion to the spinal cord. Estradiol improved locomotor function at 7, 14, 21, and 28 days post injury (DPI), when compared to control groups (measured with the BBB open field test). This effect was ER-α mediated, because functional recovery was blocked with an ER-α antagonist. We also observed that ER-α was up-regulated after SCI. Long-term treatment (28 DPI) with estradiol and Tamoxifen reduced the extent of the lesion cavity, an effect also mediated by ER-α. The antioxidant effects of estradiol were seen acutely at 2 DPI but not at 28 DPI, and this acute effect was not receptor mediated. Rats treated with Tamoxifen recovered some locomotor activity at 21 and 28 DPI, which could be related to the antioxidant protection seen at these time points. These results show that estradiol improves functional outcome, and these protective effects are mediated by the ER-α dependent and independent-mechanisms. Tamoxifen’s effects during late stages of SCI support the use of this drug as a long-term alternative treatment for this condition.

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“…Numerous studies have employed neurotrophic factors in combination with growth-supporting matrices and/or cell or tissue grafts (see McCall et al, 2012;Oudega et al, 2012 for recent reviews). Such combinations may involve the transduction of donor cell types to overexpress the particular neurotrophin(s), or as a combination through codelivery via injection or osmotic minipumps.…”

Section: Combinations Of Factorsmentioning

confidence: 99%

“…This review of the "state of play" of such growth-promoting factors tested in experimental models and clinical trials of SCI is not designed to be exhaustive, but rather is intended to distil and complement other detailed reviews to which the interested reader is also directed (e.g., Arvanian, 2013Awad, Carmody, & Steinmetz, 2015Blesch et al, 2012;Boyce & Mendell, 2014;Bregman et al, 2002;Gerin et al, 2011;Hollis, Lu, Blesch, & Tuszynski, 2009;Kabu, Gao, Kwon, & Labhasetwar, 2015;Lu & Tuszynski, 2008;McCall, Weidner, & Blesch, 2012;Oudega, Bradbury, & Ramer, 2012;Smith, Falone, & Frank, 2012;Tetzlaff et al, 2011;Weishaupt, Blesch, & Fouad, 2012). To date, provision of neurotrophic support after SCI includes some of the most commonly used neurotrophins and neuropoietic cytokines, as well as other growth factors such as glial cell-derived neurotrophic factor (GDNF), the fibroblast growth factors (FGFs), and insulin-like growth factors (IGFs).…”

Section: Introductionmentioning

confidence: 98%