Download 2016 department of medicine research day

2016 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Prevalence of gastrointestinal symptoms in TBI patients and intestinal
barrier function alteration in rats with TBI
Presenter: Million Mulugeta
Division: Digestive Diseases
☒ Faculty ☐ Fellow ☐ Resident ☐ Post-doc Research Fellow ☐ Graduate Student ☐ Medical Student ☐Other
Principal Investigator/Mentor: Million Mulugeta
Pannizoni K, Wallis RA, Tillisch K, Scremin O
Thematic Poster Category:
Atherosclerosis
Co-Investigators: Biraud M, Moussaiwi N, Larauche M, Wu V, Oh S,
Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and
Abstract
Traumatic brain injury (TBI) is a major public health concern that causes deaths, morbidity, disability
and long term care. One of the common systemic sequels of TBI is altered bowel habit. However
scientific evidence on the impact and mechanism of TBI on gut dysfunction is scarce. We aimed 1) to
determine the prevalence of gastrointestinal symptoms in TBI patients and 2) identify the underlying
alterations and key mechanisms of intestinal neuroimmune and mucosal barrier functions and related
behavioral consequences in rats.
Method: Retrospective assessment of abdominal symptoms (diarrhea, constipation, abdominal pain,
altered bowel habits and gas-indigestion) in two anonymous cohorts: 1) TBI patients at the Greater
Los Angeles Healthcare System. After exclusion for headache and medications with effects on gut
functions (constipation/diarrhea), 72 TBI patients’ (42 blast TBI and 32 non-blast TBI) data was
anonymously evaluated for prevalence of constipation and/or diarrhea. 2) In a second and separate
cohort of 19 (18 male, 1 female, mean age 36 years old) TBI patients at UCLA/VA Greater Los Angeles
Healthcare system recruited for headache and brain imaging studies, anonymous data collected using
public health questionnaire-15 (PHQ-15) somatic symptom score for gastrointestinal symptoms was
analyzed. Preclinical studies in control and TBI rats studied the histology and intestinal barrier function
using oral FD4 dye permeation in vivo.
Result: Of the 72 subjects with TBI, a mean 77.8±5.1% (n = 56) had abdominal symptoms including
diarrhea or constipation. In subjects with post-TBI diarrhea (n=32), 56.2 ± 4.2% (n = 18) had blastTBI, while 43.8 ± 5.1% (n = 14) had non-blast TBI. In subjects with post-TBI constipation (n=40),
60.0 ± 5.2% (n = 24) had blast-TBI, while 40.0 ± 5.8% (n = 16) had non-blast TBI. In the 2nd
cohort of 19 TBI patients 37-47% of the patient report little to a lot abdominal pain, altered bowel
habit (constipation/diarrhea) and indigestion and gas. Overall 65% had at least one of the three GIT
symptoms surveyed. The altered bowel habits and gas/indigestion each was significantly correlated
with headache impact score and each of the three abdominal symptoms is correlated with the PHQ-15
score. However other symptoms such as chest pain were not associated with headache suggesting
that the abdominal symptoms reported are not part of a generalized pain disorder. In rats, bTBI
caused intestinal mucosal microheamorrhage and increased intestinal permeability at 4, 24 and 7 days
post TBI from by 100-500%, with a peak barrier breach at 4h post TBI. The intestinal permeability
response is mitigated by pretreatments with myosine light chain kinase (MLCK) inhibitor or anti TNFa.
Conclusion: Given that the abdominal symptoms such as abdominal pain, constipation, diarrhea, gas,
indigestion occur in 10-15% of the general public, the close to 80% (cohort 1) and 65% (cohort 2) gut
symptoms in TBI patients suggest that gastrointestinal symptoms among TBI patients is important
that needs further study and care. The preclinical data provides a functional evidence that bTBI causes
intestinal mucosal barrier breach that involves mucosal tight junction proteins and TBf-a pathways.