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Advanced Neurology Aging blood-brain barrier in stroke

of delivery, and improve clinical outcomes . Accordingly, 2. Latour LL, Kang DW, Ezzeddine MA, et al., 2004, Early
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elderly ischemic stroke patients would greatly benefit from blood-brain barrier disruption in human focal brain
therapeutics that reduce the inflammatory degradation of ischemia. Ann Neurol, 56: 468–477.
the BBB and boost the efficacy of current treatment options 3. Bivard A, Kleinig T, Churilov L, et al., 2020, Permeability
(such as tPA) by supporting BBB integrity. measures predict hemorrhagic transformation after
ischemic stroke. Ann Neurol, 88: 466–476.
5. Conclusions 4. Brouns R, Wauters A, De Surgeloose D, et al., 2011,
Ischemic stroke is prevalent in all age groups. Ischemic Biochemical markers for blood-brain barrier dysfunction in
stroke contributes to severe BBB degradation, which is acute ischemic stroke correlate with evolution and outcome.
associated with worse prognoses, edema, and hemorrhagic Eur Neurol, 65: 23–31.
transformation. Age not only influences the features of 5. Daneman R, Prat A, 2015, The blood-brain barrier. Cold
ischemic stroke but also how the BBB is affected after Spring Harb Perspect Biol, 7: a020412.
injury. This can be explained by age-specific cellular 6. Abdullahi W, Tripathi D, Ronaldson PT, 2018, Blood-brain
and molecular mechanisms of BBB degradation, such barrier dysfunction in ischemic stroke: Targeting tight
as increases in the loss of tight junctions, immune cell junctions and transporters for vascular protection. Am J
infiltration, neutrophilic responses, MMP-9 activity, Physiol Cell Physiol, 315: C343–C356.
release of inflammatory cytokines, and oxidative stress. 7. Jiang X, Andjelkovic AV, Zhu L, et al., 2018, Blood-brain
Elderly populations are at a greater risk of more substantial barrier dysfunction and recovery after ischemic stroke. Prog
BBB damage after ischemic injury due to ischemia-induced Neurobiol, 163–164: 144–171.
cellular and molecular mechanisms of BBB degradation 8. Kanji M, Atsuo F, Hajime T, et al., 1997, Vulnerability to
that occur to a greater extent than that observed in younger cerebral hypoxic-ischemic insult in neonatal but not in adult
adults. Such degradation is exacerbated by age-related rats is in parallel with disruption of the blood-brain barrier.
comorbid health conditions, such as diabetes and AD. As Stroke, 28: 2281–2289.
such, with the BBB mediating the delivery and efficacy of 9. DiNapoli VA, Huber JD, Houser K, et al., 2008, Early
ischemic stroke treatment, new stroke therapies that may disruptions of the blood-brain barrier may contribute to
be more beneficial to vulnerable patient populations, with exacerbated neuronal damage and prolonged functional
special emphasis on selectively inhibiting the neutrophilic recovery following stroke in aged rats. Neurobiol Aging,
response, are required. Current research is highlighting the 29: 753–764.
potential of BBB maintenance following ischemic stroke as 10. Boot E, Ekker MS, Putaala J, et al., 2020, Ischaemic stroke
a therapeutic avenue. Therefore, age-dependent post-stroke in young adults: A global perspective. J Neurol Neurosurg
BBB characteristics should be taken into consideration Psychiatry, 91(4): 411–417.
to better improve current and future ischemic stroke 11. Renna R, Pilato F, Profice P, et al., 2014, Risk factor and
therapeutics. etiology analysis of ischemic stroke in young adult patients.
Acknowledgments J Stroke Cerebrovasc Dis, 23: e221–e227.
12. Tarja P, Timo E, Risto V, et al., 1997, Comparison of stroke
This work was supported by Canadian Institutes of Health features and disability in daily life in patients with ischemic
Research (CIHR- PJT-153155) to Z-P.F. S.E. was a recipient stroke aged 55 to 70 and 71 to 85 years. Stroke, 28: 729–735.
of Ontario Graduate Scholarship (Doctoral).
13. Stack CA, Cole JW, 2018, Ischemic stroke in young adults.
Conflict of interest Curr Opin Cardiol, 33: 594–604.
14. Rojas JI, Zurrú MC, Romano M, et al., 2007, Acute ischemic
The authors declare no conflict of interests. stroke and transient ischemic attack in the very old-risk
Author contributions factor profile and stroke subtype between patients older than
80 years and patients aged less than 80 years. Eur J Neurol,
Conceptualization: Zhong-Ping Feng 14: 895–899.
Writing – original draft: Sarah Eide 15. Arnold M, Halpern M, Meier N, et al., 2008, Age-dependent
Writing – review and editing: All authors differences in demographics, risk factors, co-morbidity,
etiology, management, and clinical outcome of acute
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