Dichotomous locomotor recoveries are predicted by acute changes in segmental blood flow after thoracic spinal contusion injuries in pigs

Andrea J. Santamaria, Francisco D. Benavides, Kyle Padgett, Luis G. Guada, Yohjan Nunez-Gomez, Juan Solano, James D Guest

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Neuroimaging facilitates the translation of animal pre-clinical research to human application. The large porcine spinal cord is useful for testing invasive interventions. Ideally, the safety and efficacy of a delayed intervention is tested in pigs that have recovered sufficiently after spinal cord injury (SCI) to allow either deterioration or improvement of function to be detected. We set out to create moderate severity T9 injuries in Yucatan minipigs by conducting a bridging study adapting methods previously developed in infant piglets. The injury severity was varied according to two pneumatic impactor parameters: the piston compression depth into tissue or the velocity. To stratify locomotor recovery, a 10-point scale used in prior piglet studies was redefined through longitudinal observations of spontaneous recovery. Using hindlimb body weight support to discriminate injury severity, we found that end-point recovery was strongly bimodal to either non-weight-bearing plegia with reciprocating leg movements (<5/10) or recovery of weight bearing that improved toward a ceiling effect (≥ 8/10). No intermediate recovery animals were observed at 2 months post-injury. The ability of intra-operative ultrasound and acute magnetic resonance imaging (MRI) to provide immediate predictive feedback regarding tissue and vascular changes following SCI was assessed. There was an inverse association between locomotor outcome and early gray matter hemorrhage on MRI and ultrasound. Epicenter blood flow following contusion predicted recovery or non-recovery of weight-bearing. The depth of the dorsal cerebrospinal fluid space, which varied between animals, influenced injury severity and confounded the results in this fixed-stroke paradigm.

Original languageEnglish (US)
Pages (from-to)1399-1415
Number of pages17
JournalJournal of neurotrauma
Volume36
Issue number9
DOIs
StatePublished - May 1 2019

Fingerprint

Spinal Injuries
Thoracic Injuries
Contusions
Swine
Wounds and Injuries
Weight-Bearing
Spinal Cord Injuries
Magnetic Resonance Imaging
Miniature Swine
Hindlimb
Neuroimaging
Paralysis
Blood Vessels
Cerebrospinal Fluid
Leg
Spinal Cord
Stroke
Body Weight
Hemorrhage
Safety

Keywords

  • blood flow
  • cerebrospinal fluid
  • locomotor score
  • MRI
  • spinal cord injury
  • ultrasound

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Dichotomous locomotor recoveries are predicted by acute changes in segmental blood flow after thoracic spinal contusion injuries in pigs. / Santamaria, Andrea J.; Benavides, Francisco D.; Padgett, Kyle; Guada, Luis G.; Nunez-Gomez, Yohjan; Solano, Juan; Guest, James D.

In: Journal of neurotrauma, Vol. 36, No. 9, 01.05.2019, p. 1399-1415.

Research output: Contribution to journalArticle

@article{d1b2dccc29314676946e9efc3415b4c6,
title = "Dichotomous locomotor recoveries are predicted by acute changes in segmental blood flow after thoracic spinal contusion injuries in pigs",
abstract = "Neuroimaging facilitates the translation of animal pre-clinical research to human application. The large porcine spinal cord is useful for testing invasive interventions. Ideally, the safety and efficacy of a delayed intervention is tested in pigs that have recovered sufficiently after spinal cord injury (SCI) to allow either deterioration or improvement of function to be detected. We set out to create moderate severity T9 injuries in Yucatan minipigs by conducting a bridging study adapting methods previously developed in infant piglets. The injury severity was varied according to two pneumatic impactor parameters: the piston compression depth into tissue or the velocity. To stratify locomotor recovery, a 10-point scale used in prior piglet studies was redefined through longitudinal observations of spontaneous recovery. Using hindlimb body weight support to discriminate injury severity, we found that end-point recovery was strongly bimodal to either non-weight-bearing plegia with reciprocating leg movements (<5/10) or recovery of weight bearing that improved toward a ceiling effect (≥ 8/10). No intermediate recovery animals were observed at 2 months post-injury. The ability of intra-operative ultrasound and acute magnetic resonance imaging (MRI) to provide immediate predictive feedback regarding tissue and vascular changes following SCI was assessed. There was an inverse association between locomotor outcome and early gray matter hemorrhage on MRI and ultrasound. Epicenter blood flow following contusion predicted recovery or non-recovery of weight-bearing. The depth of the dorsal cerebrospinal fluid space, which varied between animals, influenced injury severity and confounded the results in this fixed-stroke paradigm.",
keywords = "blood flow, cerebrospinal fluid, locomotor score, MRI, spinal cord injury, ultrasound",
author = "Santamaria, {Andrea J.} and Benavides, {Francisco D.} and Kyle Padgett and Guada, {Luis G.} and Yohjan Nunez-Gomez and Juan Solano and Guest, {James D}",
year = "2019",
month = "5",
day = "1",
doi = "10.1089/neu.2018.6087",
language = "English (US)",
volume = "36",
pages = "1399--1415",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "9",

}

TY - JOUR

T1 - Dichotomous locomotor recoveries are predicted by acute changes in segmental blood flow after thoracic spinal contusion injuries in pigs

AU - Santamaria, Andrea J.

AU - Benavides, Francisco D.

AU - Padgett, Kyle

AU - Guada, Luis G.

AU - Nunez-Gomez, Yohjan

AU - Solano, Juan

AU - Guest, James D

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Neuroimaging facilitates the translation of animal pre-clinical research to human application. The large porcine spinal cord is useful for testing invasive interventions. Ideally, the safety and efficacy of a delayed intervention is tested in pigs that have recovered sufficiently after spinal cord injury (SCI) to allow either deterioration or improvement of function to be detected. We set out to create moderate severity T9 injuries in Yucatan minipigs by conducting a bridging study adapting methods previously developed in infant piglets. The injury severity was varied according to two pneumatic impactor parameters: the piston compression depth into tissue or the velocity. To stratify locomotor recovery, a 10-point scale used in prior piglet studies was redefined through longitudinal observations of spontaneous recovery. Using hindlimb body weight support to discriminate injury severity, we found that end-point recovery was strongly bimodal to either non-weight-bearing plegia with reciprocating leg movements (<5/10) or recovery of weight bearing that improved toward a ceiling effect (≥ 8/10). No intermediate recovery animals were observed at 2 months post-injury. The ability of intra-operative ultrasound and acute magnetic resonance imaging (MRI) to provide immediate predictive feedback regarding tissue and vascular changes following SCI was assessed. There was an inverse association between locomotor outcome and early gray matter hemorrhage on MRI and ultrasound. Epicenter blood flow following contusion predicted recovery or non-recovery of weight-bearing. The depth of the dorsal cerebrospinal fluid space, which varied between animals, influenced injury severity and confounded the results in this fixed-stroke paradigm.

AB - Neuroimaging facilitates the translation of animal pre-clinical research to human application. The large porcine spinal cord is useful for testing invasive interventions. Ideally, the safety and efficacy of a delayed intervention is tested in pigs that have recovered sufficiently after spinal cord injury (SCI) to allow either deterioration or improvement of function to be detected. We set out to create moderate severity T9 injuries in Yucatan minipigs by conducting a bridging study adapting methods previously developed in infant piglets. The injury severity was varied according to two pneumatic impactor parameters: the piston compression depth into tissue or the velocity. To stratify locomotor recovery, a 10-point scale used in prior piglet studies was redefined through longitudinal observations of spontaneous recovery. Using hindlimb body weight support to discriminate injury severity, we found that end-point recovery was strongly bimodal to either non-weight-bearing plegia with reciprocating leg movements (<5/10) or recovery of weight bearing that improved toward a ceiling effect (≥ 8/10). No intermediate recovery animals were observed at 2 months post-injury. The ability of intra-operative ultrasound and acute magnetic resonance imaging (MRI) to provide immediate predictive feedback regarding tissue and vascular changes following SCI was assessed. There was an inverse association between locomotor outcome and early gray matter hemorrhage on MRI and ultrasound. Epicenter blood flow following contusion predicted recovery or non-recovery of weight-bearing. The depth of the dorsal cerebrospinal fluid space, which varied between animals, influenced injury severity and confounded the results in this fixed-stroke paradigm.

KW - blood flow

KW - cerebrospinal fluid

KW - locomotor score

KW - MRI

KW - spinal cord injury

KW - ultrasound

UR - http://www.scopus.com/inward/record.url?scp=85065064887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065064887&partnerID=8YFLogxK

U2 - 10.1089/neu.2018.6087

DO - 10.1089/neu.2018.6087

M3 - Article

C2 - 30284945

AN - SCOPUS:85065064887

VL - 36

SP - 1399

EP - 1415

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 9

ER -