Abstract
Intracranial surgery causes brain damage from cortical incisions, intraoperative hemorrhage, retraction, and electrocautery; collectively these injuries have recently been coined surgical brain injury (SBI). Inflammation following SBI contributes to neuronal damage. This study develops T-cells that are immunologically tolerant to brain antigen via the exposure of myelin basic protein (MBP) to airway mucosa. We hypothesize that these T-cells will migrate to the site of corticotomy, secrete immunosuppressive cytokines, such as TGFβ1, reduce inflammation, and improve neurological outcomes following SBI. A standard model for SBI was used for this experiment. C57 mice were divided into six groups: SHAM + Vehicle, SHAM + Ovalbumin, SHAM + MBP, SBI + Vehicle, SBI + OVA, and SBI + MBP. Induction of mucosal tolerance to vehicle, ovalbumin, or MBP was performed prior to SBI. Neurological scores and TBFβ1 cytokine levels were measured 48 h postoperatively. Mice receiving craniotomy demonstrated a reduction in neurological score. Animals tolerized to MBP (SBI + MBP) had better postoperative neurological scores than SBI + Vehicle and SBI + OVA. SBI inhibited the cerebral expression TGFβ1 in PBS and OVA treated groups, whereas MBP treated-animals preserved preoperative levels. Mucosal tolerance to MBP leads to significant improvement in neurological outcome that is associated with the preservation of endogenous levels of brain TGFβ1.
Original language | English (US) |
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Title of host publication | Intracerebral Hemorrhage Research: From Bench to Bedside |
Publisher | Springer-Verlag Wien |
Pages | 283-287 |
Number of pages | 5 |
Edition | 111 |
ISBN (Print) | 9783709106921 |
DOIs | |
State | Published - 2011 |
Externally published | Yes |
Publication series
Name | Acta Neurochirurgica, Supplementum |
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Number | 111 |
ISSN (Print) | 00651419 |
ISSN (Electronic) | 00016268 |
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Keywords
- Brain injury
- Inflammation
- Mucosal tolerance
- Neuroprotection
- TGFβ1
ASJC Scopus subject areas
- Surgery
- Clinical Neurology
Cite this
Mucosal tolerance to brain antigens preserves endogenous TGFβ-1 and improves neurological outcomes following experimental craniotomy. / Jafarian, N.; Ayer, R.; Eckermann, J.; Tong, W.; Jafarian, N.; Applegate, Richard Lee; Stier, G.; Martin, R.; Tang, J.; Zhang, John H.
Intracerebral Hemorrhage Research: From Bench to Bedside. 111. ed. Springer-Verlag Wien, 2011. p. 283-287 (Acta Neurochirurgica, Supplementum; No. 111).Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - Mucosal tolerance to brain antigens preserves endogenous TGFβ-1 and improves neurological outcomes following experimental craniotomy
AU - Jafarian, N.
AU - Ayer, R.
AU - Eckermann, J.
AU - Tong, W.
AU - Jafarian, N.
AU - Applegate, Richard Lee
AU - Stier, G.
AU - Martin, R.
AU - Tang, J.
AU - Zhang, John H.
PY - 2011
Y1 - 2011
N2 - Intracranial surgery causes brain damage from cortical incisions, intraoperative hemorrhage, retraction, and electrocautery; collectively these injuries have recently been coined surgical brain injury (SBI). Inflammation following SBI contributes to neuronal damage. This study develops T-cells that are immunologically tolerant to brain antigen via the exposure of myelin basic protein (MBP) to airway mucosa. We hypothesize that these T-cells will migrate to the site of corticotomy, secrete immunosuppressive cytokines, such as TGFβ1, reduce inflammation, and improve neurological outcomes following SBI. A standard model for SBI was used for this experiment. C57 mice were divided into six groups: SHAM + Vehicle, SHAM + Ovalbumin, SHAM + MBP, SBI + Vehicle, SBI + OVA, and SBI + MBP. Induction of mucosal tolerance to vehicle, ovalbumin, or MBP was performed prior to SBI. Neurological scores and TBFβ1 cytokine levels were measured 48 h postoperatively. Mice receiving craniotomy demonstrated a reduction in neurological score. Animals tolerized to MBP (SBI + MBP) had better postoperative neurological scores than SBI + Vehicle and SBI + OVA. SBI inhibited the cerebral expression TGFβ1 in PBS and OVA treated groups, whereas MBP treated-animals preserved preoperative levels. Mucosal tolerance to MBP leads to significant improvement in neurological outcome that is associated with the preservation of endogenous levels of brain TGFβ1.
AB - Intracranial surgery causes brain damage from cortical incisions, intraoperative hemorrhage, retraction, and electrocautery; collectively these injuries have recently been coined surgical brain injury (SBI). Inflammation following SBI contributes to neuronal damage. This study develops T-cells that are immunologically tolerant to brain antigen via the exposure of myelin basic protein (MBP) to airway mucosa. We hypothesize that these T-cells will migrate to the site of corticotomy, secrete immunosuppressive cytokines, such as TGFβ1, reduce inflammation, and improve neurological outcomes following SBI. A standard model for SBI was used for this experiment. C57 mice were divided into six groups: SHAM + Vehicle, SHAM + Ovalbumin, SHAM + MBP, SBI + Vehicle, SBI + OVA, and SBI + MBP. Induction of mucosal tolerance to vehicle, ovalbumin, or MBP was performed prior to SBI. Neurological scores and TBFβ1 cytokine levels were measured 48 h postoperatively. Mice receiving craniotomy demonstrated a reduction in neurological score. Animals tolerized to MBP (SBI + MBP) had better postoperative neurological scores than SBI + Vehicle and SBI + OVA. SBI inhibited the cerebral expression TGFβ1 in PBS and OVA treated groups, whereas MBP treated-animals preserved preoperative levels. Mucosal tolerance to MBP leads to significant improvement in neurological outcome that is associated with the preservation of endogenous levels of brain TGFβ1.
KW - Brain injury
KW - Inflammation
KW - Mucosal tolerance
KW - Neuroprotection
KW - TGFβ1
UR - http://www.scopus.com/inward/record.url?scp=79960659666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960659666&partnerID=8YFLogxK
U2 - 10.1007/978-3-7091-0693-8_47
DO - 10.1007/978-3-7091-0693-8_47
M3 - Conference contribution
C2 - 21725769
AN - SCOPUS:79960659666
SN - 9783709106921
T3 - Acta Neurochirurgica, Supplementum
SP - 283
EP - 287
BT - Intracerebral Hemorrhage Research: From Bench to Bedside
PB - Springer-Verlag Wien
ER -