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Advanced Neurology Aging blood-brain barrier in stroke

BBB integrity clearly may diminish neuronal damage
and thus lead to better clinical outcomes after ischemic
stroke. Therefore, understanding the characteristics and
underlying mechanisms of BBB injury in different age
populations is crucial.

3.1. BBB structure and function following ischemic
stroke

Adults experience significant opening of the BBB shortly
after ischemic stroke, which contributes to ischemic injury.
Despite previous assumptions of a biphasic opening of
the BBB following ischemia , more recent data support
[27]
a continuous opening of the BBB that can last few days to
few weeks post-injury. For instance, adult Wistar rats that
underwent MCAO experienced continuous BBB opening
Figure 1. Risk factors and prognoses following stroke in adult and elderly with the use of small and large tracers that were observable
[28]
patients. A brief comparison of the commonly reported risk factors of beginning 25 min post-injury and lasting up to 4 weeks .
ischemic stroke in adult and elderly patients and later prognosis and Similarly, in humans, a continuously disrupted BBB was
survival. The illustration was created with BioRender.com. observed in 33% of adult patients in the first week following
[2]
[2]
disease (AD) significantly worsen the clinical outcome stroke , which began around 12.9 h post-ischemia and
[29]
of stroke in both humans and animal models [20,21] . The was reported to last up to 90.7 h . Notably, early BBB
incidence of stroke increases in AD patients , along with disruption is associated with poorer clinical outcomes that
[22]
the increased risk of a worse ischemic outcome. Dementia are significantly correlated to hemorrhagic transformation,
patients experience a two- to three-fold increased risk stroke severity, and long-term neurological scores assessed
[2-4]
of death following ischemic stroke compared with non- up to 90 days post-injury . Thus, any age-related
dementia patients, with the risk of death increasing with variations in the timing and degree of BBB injury following
the severity of dementia . Mouse models of AD further stroke may considerably affect both acute and long-term
[23]
demonstrate a significant increase in ischemic damage outcomes.
compared with non-AD controls, with amyloid precursor Elderly patients are more susceptible to ischemia-
protein overexpression resulting in significantly larger induced BBB damage than younger adult patients; this
cerebral infarcts and greater reductions in cerebral blood is also worsened by comorbid conditions prevalent in
flow [20,24] . Diabetic mouse models also demonstrate greater elderly patients. Compared with a younger BBB, an
ischemic injury and the development of more severe aged BBB exhibits numerous qualities that make it more
neurological deficits post-stroke [21,25] , potentially linked to susceptible to ischemic injury and result in a more severe
greater inflammatory responses [21,26] . Overall, the observed prognosis. This includes a large age-dependent reduction
vulnerability of the aged brain is due to a variety of age- in barrier function, which is observed in both aged animal
related physiological factors that may contribute to a weak models [9,30] and humans . Consequently, the aged BBB
[1]
BBB, including inflammatory mechanisms and a naturally undergoes earlier and more severe disruption after injury,
aging neurovascular unit. which precedes a large portion of neuronal damage [9,31] . In
fact, aged rats experience up to a two-fold greater increase
3. BBB injury following ischemic stroke in BBB permeability after ischemia compared with
Opening of the BBB after ischemia is observed in all age younger adults . Diabetes further exacerbates ischemic
[9]
groups but may vary in timing and degree of opening, BBB opening, contributing to edema and poorer clinical
which is largely thought to correlate with the degree outcomes . Diabetes significantly affects basal BBB
[32]
of injury severity and prognosis. Elevations in BBB integrity, as evident in diabetic mouse models exhibiting
permeability following injury leave the brain susceptible a 2.4-fold greater BBB permeability than non-diabetic
to blood-borne toxins, greater immune cell infiltration, controls . This translates to significantly greater BBB
[33]
[34]
inflammatory mediators, and water influx, which can leakage after ischemic stroke . Similarly, the elevated
further worsen neuronal damage and brain edema. Several susceptibility to ischemic damage associated with AD is
key cellular and molecular events correspond to BBB thought to be a result of vascular dysfunction, which is
injury following stroke, and these vary in degree and form significantly associated with BBB disruption. Cerebral
between adult and elderly patients (Figure 2). Maintaining amyloid angiopathy (CAA), which is observed universally

Volume 1 Issue 2 (2022) 3 https://doi.org/10.36922/an.v1i2.1