Name: Saroj Chakraborty

03/22/2016
Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce BloodBrain Barrier
Permeability following Experimental Traumatic Brain Injury
Dash et al

Hypothesis and Relevance:

This manuscript hypothesizes that the activation of alpha 7 cholinergic nicotinic receptors after
Traumatic brain injury (TBI) decreases blood brain barrier permeability and neuroinflammation.
For TBI, BBB permeability and neuroinflammation is a key concern. The researchers try to show
that nAChRa7 receptors are involved in reducing the effect of TBI. This work is significant
because it shows a novel pathway involved to reduce the effect of TBI. This may be used as a
potential drug to not only TBI but also other neuroinflammatory dieases.
Summary
Figure 1:
In this figure, the researchers show that loss of nAChRa7 and the level of neuroinflammatory
markers following TBI. They show a direct connection as compared with the wild type,
nAChRa7 -/- significantly increases the inflammatory cytokines level. But, this data would be
more complete if they add similar data for the splenectomied rats as they used it later stage of
experiments.
Figure 2:
Here, the authors show that loss of nAChRa7 and the level of BBB permeability following TBI.
They show a direct connection as compared with the wild type, nAChRa7 -/- significantly
decreases the BBB permeability. Similarly, this data would be more complete if they add BBB
permeability data for the splenectomied rats as they used it later stage of experiments.
Figure 3:
The researchers examine the effect of agonist of nAChRa7 on inflammatory cytokines. They find
out that it shows some positive effect, improving condition by lowering the level of
inflammatory cytokines. But, here some experiments they used mice others rats, comparison may
be wrong.
Figure 4:
Similarly, the researchers show the relationship between agonist application of nAChRa7 and the
condition of neuroinflammatory markers like MPO+ and CCR2+, find out the level of these
markers decreases indicating improvement of conditions.
Figure 5:
The researchers show the effect of agonist and allosteric modulators of nAChRa7 in loss of
nAChRa7 following TBI. Where, they found agonist of nAChRa7 have no effect on nAChRa7-/-

animals. Indicating not only the stimulator but also the receptor is responsible for that
phenomena. But, they dont include the result of allosteric modulator on nAChRa7-/- animals.
Figure 6:
The researchers try to find out how the agonist of nAChRa7 works and they tried condition of
endothelial cells and tight junction protein loss. Both of them showed significant improvement
after treatment. As they dont tested other parts like role of microglia and astroglia in BBB
permeability, may be they play a key role or may be the nAChRa7 has some direct link with
them.
Figure 7:
The researchers try to show the effect of an antagonist of nAChRa7 (alpha-Bgtx) following TBI.
The antagonist increases BBB permeability that is just opposite to the result of agonist indicating
a direct involvement of nAChRa7. After splenectomy, the effect of both agonist and antagonist
becomes similar to vehicle, which is also indicative of nAChRa7 involvement in improving
condition after TBI.
Figure 8:
The researchers try to establish a model for the paper. This is a nice work as it summarizes the
whole thing. However, very crucial part of brain that has a role in TBI related effects like
microglia, astrocytes etc are missing from the figure.
Assessment
The authors findings support that the nAChRa7 plays a key role in TBI. And it would be a
wonderful drug target as the agonist of nAChRa7 showing improvement in both BBB
permeability and reducing the level of inflammatory cytokines and markers. However, there is a
problem with that, as nACh receptors are found in many places in our body, it may show side
effects. Overall, the paper establish their idea in a very proper way, but some of the question that
arises are-what are the role of other part of the brain? nAChRa7, that present in many other brain
part, what is the effect on them to the application of an agonist? It also paved a way to do some
experiments that would clarify the idea. But, overall, they establish their hypothesis very well
and it contains a novel finding that is a good starting point for finding a treatment for TBI.