Blood-brain barrier injury: implications and management in stroke

The blood-brain barrier (BBB) is a vital structure that protects the brain by tightly regulating which substances can pass from the bloodstream into brain tissue. However, under conditions such as stroke, this barrier can become compromised, threatening the integrity of the central nervous system and exacerbating brain damage.

What is the blood-brain barrier and how does it work?

The BBB is composed of tightly joined endothelial cells surrounded by astrocytes and pericytes, acting as a selective filter. Its main function is:

1. To protect the brain: it blocks the passage of toxins and microorganisms.
2. To regulate the brain environment: it allows the entry of essential nutrients and removes metabolic waste.
3. To maintain cerebral homeostasis: it preserves a stable chemical environment for neuronal function.

Blood-brain barrier injury in stroke

In stroke, whether ischemic or hemorrhagic, the interruption of blood flow and inflammation can damage the BBB, resulting in:

1. Increased permeability: toxic substances and immune cells enter the brain, causing inflammation and neuronal damage.
2. Cerebral edema: fluid leakage into brain tissue causes swelling, increasing intracranial pressure.
3. Enhancement of secondary damage: it facilitates excitotoxicity and oxidative stress, worsening the initial injury.

Causes of blood-brain barrier injury

BBB injury can occur in various neurological conditions, with stroke being one of the main causes. The most common causes include:

1. Ischemic stroke:
   • The lack of oxygen triggers the release of free radicals and inflammatory mediators that damage the barrier.
2. Cerebral hemorrhage:
   • The rupture of blood vessels exerts a direct toxic effect on endothelial cells.
3. Traumatic brain injury:
   • Physical impact can disrupt the integrity of the BBB.
4. Infections and inflammatory diseases:
   • Pathogens such as the Zika virus or diseases like multiple sclerosis impair the barrier.
5. Chronic hypertension:
   • Ongoing damage to blood vessels can compromise BBB function.

Clinical consequences of blood-brain barrier injury

When the BBB is damaged, the brain becomes vulnerable to multiple complications, including:

• Inflammation and oxidative stress: contribute to progressive neuronal damage.
• Cerebral edema: can lead to brain herniation in severe cases.
• Cognitive impairment: associated with chronic neuroinflammation.
• Increased risk of infections: altered permeability facilitates the entry of pathogens.

Diagnosis of blood-brain barrier injury

Although not always easy to detect, BBB assessment is performed using advanced methods:

1. Magnetic resonance imaging (MRI):
   • Identifies cerebral edema and areas of increased permeability.
2. Positron emission tomography (PET):
   • Measures metabolic activity and areas of inflammation in the brain.
3. Biomarkers:
   • Specific proteins, such as albumin in cerebrospinal fluid, indicate barrier damage.
4. Neuropsychological tests:
   • Assess functional impact on memory, attention, and other cognitive domains.

Treatment of blood-brain barrier injury

Management of BBB injury involves controlling the underlying cause and limiting secondary damage:

1. Stroke management:
   • Reperfusion in ischemic stroke through thrombolysis or mechanical thrombectomy.
   • Bleeding control in hemorrhagic stroke.
2. Anti-inflammatory therapies:
   • Drugs such as corticosteroids can reduce brain inflammation.
3. Antioxidants:
   • Compounds that neutralize free radicals and protect endothelial cells.
4. Experimental therapies:
   • Gene therapies: aim to repair damage at the cellular level.
   • Nanocarriers: systems that protect specific drugs to cross the BBB without damaging it.

Prevention of blood-brain barrier damage

Maintaining BBB health is key to reducing the risk of neurological diseases. Preventive strategies include:

• Control of cardiovascular risk factors such as hypertension and diabete
• Prevention of infections and early treatment of inflammatory diseases.
• Healthy lifestyle, including an antioxidant-rich diet and regular exercise.

Conclusion

Blood-brain barrier injury is a critical factor in the progression of stroke and other neurological disorders. Early identification and treatment are essential to limit brain damage and improve clinical outcomes.

With advances in neuroprotective therapies and precision diagnostics, the management of this condition continues to evolve, offering new hope for preserving brain health and preventing long-term complications.

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