Cerebrospinal fluid may mediate CNS ischemic injury

Wang, Yanming F.; Gwathmey, Judith K.; Zhang, Guorong; Soriano, Sulpicio G.; He, Shunli; Wang, Yanguang

doi:10.1186/1743-8454-2-7

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…Functional motor recovery has been identified when Alb is injected directly into the spinal tissue or via the intravenous route [21], but careful analysis should be performed with FITC-albumin injected via the intrathecal route which would address this concern. Indeed a similar study has identified both grey and white spinal matter labelling with FITC-albumin when administered via the intravenous route, confirming penetration at least into the intraspinal microcirculatory system [87]. Albumin is commonly used a drug delivery system in the clinical setting [88] and specific known binding sites with OA suggest a biological basis for the synergistic action between both molecules observed in this study [89].…”

Section: Discussionsupporting

confidence: 77%

“…Albumin most probably provides therapeutic benefits for spinal cord injury when administered alone [21] . Indeed the replacement of cerebrospinal fluid with 8% albumin following experimental ischaemic experimental SCI can reduce motor deficits, although this has been attributed mainly to reduction of intraspinal oedema [87] . However evidence for direct penetrability of Alb-OA into the spinal parenchyma should be addressed in future studies.…”

Section: Discussionmentioning

confidence: 99%

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Treatment of Rat Spinal Cord Injury with the Neurotrophic Factor Albumin-Oleic Acid: Translational Application for Paralysis, Spasticity and Pain

et al. 2011

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Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often characterized by the debilitating symptoms of paralysis, spasticity and pain, which require treatment with novel pleiotropic pharmacological agents. Previous in vitro studies suggest that Albumin (Alb) and Oleic Acid (OA) may play a role together as an endogenous neurotrophic factor. Although Alb can promote basic recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on a known translational measure of SCI associated with symptoms of spasticity and change in nociception has not been studied. Following T9 spinal contusion injury in Wistar rats, intrathecal treatment with: i) Saline, ii) Alb (0.4 nanomoles), iii) OA (80 nanomoles), iv) Alb-Elaidic acid (0.4/80 nanomoles), or v) Alb-OA (0.4/80 nanomoles) were evaluated on basic motor function, temporal summation of noxious reflex activity, and with a new test of descending modulation of spinal activity below the SCI up to one month after injury. Albumin, OA and Alb-OA treatment inhibited nociceptive Tibialis Anterior (TA) reflex activity. Moreover Alb-OA synergistically promoted early recovery of locomotor activity to 50±10% of control and promoted de novo phasic descending inhibition of TA noxious reflex activity to 47±5% following non-invasive electrical conditioning stimulation applied above the iSCI. Spinal L4–L5 immunohistochemistry demonstrated a unique increase in serotonin fibre innervation up to 4.2±1.1 and 2.3±0.3 fold within the dorsal and ventral horn respectively with Alb-OA treatment when compared to uninjured tissue, in addition to a reduction in NR1 NMDA receptor phosphorylation and microglia reactivity. Early recovery of voluntary motor function accompanied with tonic and de novo phasic descending inhibition of nociceptive TA flexor reflex activity following Alb-OA treatment, mediated via known endogenous spinal mechanisms of action, suggests a clinical application of this novel neurotrophic factor for the treatment of paralysis, spasticity and pain.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Treatment of Rat Spinal Cord Injury with the Neurotrophic Factor Albumin-Oleic Acid: Translational Application for Paralysis, Spasticity and Pain

et al. 2011

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“…However, the naloxone effect might be mediated by suppression of excitatory neurotransmitters, and SFD might work by removing substances toxic to ischemic neurons (ie, endorphins, excitatory neurotransmitters, or other substances), thereby acting on the same final injury pathway. 21,22 We added barbiturate burst suppression in 1989 coincident with the elimination of nitroprusside for blood pressure control because of its negative effect on spinal cord blood flow and organ perfusion. 1,23,24 We also became more aggressive with moderate hypothermia, and by 1989, our protocol called for the core temperature to be less than 34 C before aortic occlusion; the core temperature decreased to 32 C to 33 C, an additional 1.5 C to 2 C, with cold renal perfusion.…”

mentioning

confidence: 99%

It is not just assisted circulation, hypothermic arrest, or clamp and sew

Acher

2010

The Journal of Thoracic and Cardiovascular Surgery

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We have surgically treated 771 patients for thoracic and thoracoabdominal aortic aneurysms since 1983. Our primary effort has been to develop experimentally validated strategies to reduce paraplegia, renal failure, and mortality in these high-risk patients. This approach has led to a spinal cord protection protocol that has reduced paraplegia risk by 80% (observed/expected ratio = 0.19) with the use of cerebral spinal fluid drainage, moderate hypothermia (31°C-33°C), endorphin receptor antagonist (naloxone), and thiopental burst suppression while optimizing mean arterial pressure (> 90 mm Hg) and cardiac index. The elective mortality rate is 2.80% (17% for acute patients), and with rapid renal cooling for renal protection, only 0.88% required permanent dialysis. These results were achieved without the use of assisted circulation. We have reattached intercostal arteries since 2005 using preoperative magnetic resonance angiographic localization, but it remains unclear whether intercostal reimplantation reduces paraplegia risk, as we had initially proposed. We strongly believe that a consistent anesthetic and postoperative care protocol uniformly built and applied around these principles greatly enhances our surgical outcomes. We also show that improved outcomes with assisted circulation and hypothermic arrest in treatment of thoracoabdominal aortic disease follow similar principles of spinal cord and end-organ protection.

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“…2 Certainly the pressure environment of the spinal cord critically influences neurological function, and so, under experimental conditions, relatively small absolute alterations in CSF pressure may have profound implications for how the spinal cord responds to insult. 3,4 However, it remains to be determined if vertebral position and/or motion within physiological limits alter CSF pressure and, furthermore, if SMT influences CSF pressure.…”

mentioning

confidence: 99%