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Effects of Traumatic Brain Injury Reversed (in Mice)

posted by mrpg on Tuesday July 11 2017, @08:01AM   
from the pinky-and-the-brain dept.

takyon writes:

A compound called the Integrated Stress Response inhibitor (ISRIB) may restore memory by reversing the effects of traumatic brain injury (in mice):

Whether caused by a car accident that slams your head into the dashboard or repeated blows to your cranium from high-contact sports, traumatic brain injury can be permanent. There are no drugs to reverse the cognitive decline and memory loss, and any surgical interventions must be carried out within hours to be effective, according to the current medical wisdom. But a compound previously used to enhance memory in mice may offer hope: Rodents who took it up to a month after a concussion had memory capabilities similar to those that had never been injured.

The study "offers a glimmer of hope for our traumatic brain injury patients," says Cesario Borlongan, a neuroscientist who studies brain aging and repair at the University of South Florida in Tampa. Borlongan, who reviewed the new paper, notes that its findings are especially important in the clinic, where most rehabilitation focuses on improving motor—not cognitive—function.

[...] In 2013, the lab of Peter Walter, a biochemist at the University of California, San Francisco (UCSF), discovered a compound—called ISRIB—that blocked the stress response in human cells in a dish. Surprisingly, when tested in healthy mice, ISRIB boosted their memory. Wondering whether the drug could also reverse memory impairment, Walter teamed up with UCSF neuroscientist Susanna Rosi to study mouse models of traumatic brain injury. First, they showed that the stress response remains active in the hippocampus, a brain region important for learning and memory, for at least 28 days in injured mice. And they wondered whether administering ISRIB would help.

Rosi and her team first used mechanical pistons to hit anesthetized mice in precise parts of their surgically exposed brains, resulting in contusive injuries, focused blows that can also result from car accidents or being hit with a heavy object. After 4 weeks of rest, Rosi trained the mice to swim through a water maze, where they used cues to remember the location of a hidden resting platform. Healthy mice got better with practice, but the injured ones didn't improve. However, when the injured mice were given ISRIB 3 days in a row, they were able to solve the maze just as quickly as healthy mice up to a week later [open, DOI: 10.1073/pnas.1707661114] [DX], the researchers report today in the Proceedings of the National Academy of Sciences.

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Original Submission

• "All animals fully recovered..." (Score: 0) by Anonymous Coward on Tuesday July 11 2017, @07:27PM

  by Anonymous Coward on Tuesday July 11 2017, @07:27PM (#537754)

  Surgical Procedure. All animals were randomly assigned to TBI or sham surgeries. Animals were anesthetized and maintained at 2% isoflurane and secured to a stereotaxic frame with nontraumatic ear bars. The hair on their scalp was removed, and eye ointment and betadine were applied to their eyes and scalp, respectively. A midline incision was made to expose the skull.

  Concussive TBI: Closed Head Injury. TBI was induced along the midline of the parietal lobe using the closed head injury model (38). The head of the animal was supported with foam before injury. Contusion was induced using a 5-mm convex tip attached to an electromagnetic impactor (Leica) at the following coordinates: anteroposterior, −1.50 mm and mediolateral, 0 mm with respect to bregma. The contusion was produced with an impact depth of 1 mm from the surface of the skull with a velocity of 5.0 m/s sustained for 300 ms. Any animals that had a fractured skull after injury were excluded from the study. Sham animals received the midline skin incision but no impact.

  After focal or concussive TBI surgery, the scalp was sutured and the animal was allowed to recover in an incubation chamber set to 37 °C. Animals were returned to their home cage after showing normal walking and grooming behavior. All animals fully recovered from the surgical procedures as exhibited by normal behavior and weight maintenance monitored throughout the duration of the experiments.

  http://www.pnas.org/cgi/doi/10.1073/pnas.1707661114 [pnas.org]

  I don't see why they claim all animals fully recovered when they had to exclude an unknown amount due to skull fractures. Probably related, they write:

  all behaviors were run on independent animal cohorts.

  So were there many mice that received very severe injuries but just a few that had minor ones ? I originally took a look because I wanted to see how they judged that the damage was consistent across groups. They don't seem to have checked that at all, and from this description it appears to vary wildly (from fractured skull and has to be dropped from the study to "fully recovered").

  It also isn't clear whether the post-mortem electrophysiology was done on mice that were also tested for behavior in some way. If so, where is the scatter chart of their supposed cause and effect? If not, that seems like a waste of animals to me (which, besides being bad science, is a federal crime).

  Also it is weird to see them mention at the beginning of that quote that "nontraumatic ear bars" were used for this procedure.