Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

Peter J Crack, Moses Zhang, Maria Cristina Morganti-Kossmann, Andrew Morris, Jonathan M Wojciak, Jonathan K Fleming, Ila Karve, David K Wright, Maithili Sashindranath, Yona Goldshmit, Alison Conquest, Maria Daglas, Leigh Andrea Johnston, Robert Lindsay Medcalf, Roger A Sabbadini, Alice Pebay

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37 Citations (Scopus)

Abstract

Background: Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. FINDINGS: Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions: This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.
Original languageEnglish
Pages (from-to)1 - 11
Number of pages11
JournalJournal of Neuroinflammation
Volume11
Issue number(Art. No: 37)
DOIs
Publication statusPublished - 2014

Cite this

Crack, P. J., Zhang, M., Morganti-Kossmann, M. C., Morris, A., Wojciak, J. M., Fleming, J. K., ... Pebay, A. (2014). Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes. Journal of Neuroinflammation, 11((Art. No: 37)), 1 - 11. https://doi.org/10.1186/1742-2094-11-37
Crack, Peter J ; Zhang, Moses ; Morganti-Kossmann, Maria Cristina ; Morris, Andrew ; Wojciak, Jonathan M ; Fleming, Jonathan K ; Karve, Ila ; Wright, David K ; Sashindranath, Maithili ; Goldshmit, Yona ; Conquest, Alison ; Daglas, Maria ; Johnston, Leigh Andrea ; Medcalf, Robert Lindsay ; Sabbadini, Roger A ; Pebay, Alice. / Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes. In: Journal of Neuroinflammation. 2014 ; Vol. 11, No. (Art. No: 37). pp. 1 - 11.
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title = "Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes",
abstract = "Background: Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. FINDINGS: Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions: This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.",
author = "Crack, {Peter J} and Moses Zhang and Morganti-Kossmann, {Maria Cristina} and Andrew Morris and Wojciak, {Jonathan M} and Fleming, {Jonathan K} and Ila Karve and Wright, {David K} and Maithili Sashindranath and Yona Goldshmit and Alison Conquest and Maria Daglas and Johnston, {Leigh Andrea} and Medcalf, {Robert Lindsay} and Sabbadini, {Roger A} and Alice Pebay",
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language = "English",
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Crack, PJ, Zhang, M, Morganti-Kossmann, MC, Morris, A, Wojciak, JM, Fleming, JK, Karve, I, Wright, DK, Sashindranath, M, Goldshmit, Y, Conquest, A, Daglas, M, Johnston, LA, Medcalf, RL, Sabbadini, RA & Pebay, A 2014, 'Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes', Journal of Neuroinflammation, vol. 11, no. (Art. No: 37), pp. 1 - 11. https://doi.org/10.1186/1742-2094-11-37

Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes. / Crack, Peter J; Zhang, Moses; Morganti-Kossmann, Maria Cristina; Morris, Andrew; Wojciak, Jonathan M; Fleming, Jonathan K; Karve, Ila; Wright, David K; Sashindranath, Maithili; Goldshmit, Yona; Conquest, Alison; Daglas, Maria; Johnston, Leigh Andrea; Medcalf, Robert Lindsay; Sabbadini, Roger A; Pebay, Alice.

In: Journal of Neuroinflammation, Vol. 11, No. (Art. No: 37), 2014, p. 1 - 11.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

AU - Crack, Peter J

AU - Zhang, Moses

AU - Morganti-Kossmann, Maria Cristina

AU - Morris, Andrew

AU - Wojciak, Jonathan M

AU - Fleming, Jonathan K

AU - Karve, Ila

AU - Wright, David K

AU - Sashindranath, Maithili

AU - Goldshmit, Yona

AU - Conquest, Alison

AU - Daglas, Maria

AU - Johnston, Leigh Andrea

AU - Medcalf, Robert Lindsay

AU - Sabbadini, Roger A

AU - Pebay, Alice

PY - 2014

Y1 - 2014

N2 - Background: Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. FINDINGS: Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions: This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.

AB - Background: Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. FINDINGS: Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions: This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.

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U2 - 10.1186/1742-2094-11-37

DO - 10.1186/1742-2094-11-37

M3 - Article

VL - 11

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EP - 11

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

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ER -