Blocking Opioid Receptors Improved Blood Flow After Traumatic Brain Injury
An opioid receptor blocker improved cerebral blood flow, blood pressure, and EEG recovery after brain injury — and the active form outperformed its inactive mirror image.
Quick Facts
What This Study Found
Dynorphin A accumulated in injured brain regions after fluid-percussion brain injury in cats. These same regions showed significant decreases in cerebral blood flow. Enkephalin did not accumulate.
The opioid antagonist Win-(-), given 15 minutes after injury, significantly improved multiple outcomes: mean arterial blood pressure increased, EEG amplitude (brain wave activity) improved, regional cerebral blood flow recovered, and both the severity and incidence of brain hemorrhage decreased. Survival after injury was significantly better.
The control was elegant: Win-(+), the mirror-image version of the same drug that cannot bind opioid receptors, had no effect. Neither did saline. This confirmed the benefits came specifically from blocking opioid receptors.
Key Numbers
How They Did This
Cats received fluid-percussion brain injury. Treatment groups received Win-(-) (active opioid antagonist), Win-(+) (inactive control), or saline at 15 minutes after injury. Outcomes measured: blood pressure, EEG amplitude, regional cerebral blood flow (using radioactive microspheres), hemorrhage incidence, and survival. Dynorphin and enkephalin were measured in brain regions. Tested in cats, not people.
Why This Research Matters
This was strong preclinical evidence that blocking opioid receptors after brain trauma can improve outcomes. The use of an inactive mirror-image control made the results convincing. The findings supported clinical trials of opioid antagonists for traumatic brain injury.
The Bigger Picture
This companion study to RPEP-00021 moved from correlation to treatment. By showing that blocking opioid receptors improved outcomes, it provided direct evidence for opioid peptides as therapeutic targets in brain trauma.
What This Study Doesn't Tell Us
Tested in cats, not people. Treatment was given at 15 minutes post-injury, which is faster than typical emergency room arrival. Infarct size and 24-hour mortality were not significantly different from controls, meaning some key outcomes did not improve. Translating large-animal brain injury results to humans is uncertain.
Questions This Raises
- ?What is the optimal treatment window for opioid blockers after brain injury?
- ?Would selective kappa receptor blockers work better?
Trust & Context
- Key Stat:
- Improved blood flow and EEG With opioid receptor blocker given 15 min after brain injury
- Evidence Grade:
- Moderate animal study with active vs inactive stereoisomer control — a rigorous pharmacological design.
- Study Age:
- Published in 1987 — key study driving interest in opioid antagonists for TBI treatment.
- Original Title:
- Endogenous opioids may mediate secondary damage after experimental brain injury.
- Published In:
- The American journal of physiology, 253(5 Pt 1), E565-74 (1987)
- Authors:
- McIntosh, T K(3), Hayes, R L, DeWitt, D S, Agura, V, Faden, A I
- Database ID:
- RPEP-00052
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is a stereoisomer control?
Win-(+) is the mirror-image form of the drug that cannot bind to opioid receptors. Using it as a control proves the effect comes specifically from blocking opioid receptors, not from other drug properties.
Has this been tried in humans?
Yes — naloxone (an opioid blocker) has been tested in human TBI trials with mixed results. The principle is validated but finding the right drug, dose, and timing remains challenging.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-00052APA
McIntosh, T K; Hayes, R L; DeWitt, D S; Agura, V; Faden, A I. (1987). Endogenous opioids may mediate secondary damage after experimental brain injury.. The American journal of physiology, 253(5 Pt 1), E565-74.
MLA
McIntosh, T K, et al. "Endogenous opioids may mediate secondary damage after experimental brain injury.." The American journal of physiology, 1987.
RethinkPeptides
RethinkPeptides Research Database. "Endogenous opioids may mediate secondary damage after experi..." RPEP-00052. Retrieved from https://rethinkpeptides.com/research/mcintosh-1987-endogenous-opioids-may-mediate
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.