Traumatic brain injury (TBI) occurs when a sudden trauma causes damage to the brain. It can result from a violent jolt to the head or when an object pierces the skull and enters brain tissue. Injury that occurs minutes or days after the initial trauma is called secondary injury (eg. changes in cerebral flood flow and pressure within the skull).[1] Symptoms can vary depending on the nature of the injury and can include certain physical, cognitive, emotional, social, and behavioural effects. Common causes include falls, vehicle collisions, violence, sports injuries, explosive blasts, and other combat injuries. Approximately, 1.1 million Americans are treated for traumatic brain injury annually and some 50,000 of those die from their injuries.[2] Consequently, TBI has been the focus of increasing medical research into the implications of such injuries on development, cognition, underlying biological mechanisms of the brain, and proper preventive treatment. TBI can be classified according to severity, age groups affected, mechanism (eg. closed or penetrating), anatomical features (eg. localization to either whole brain structures or individual neurons), or other relevant criteria.

Mild traumatic brain injury, or concussion, is widely known to be the most frequent type of TBI and occurs when the brain moves and impacts against the skull (coup and countercoup) due to a collision of the head and can result in temporary neurological dysfunction. Concussions are among the most frequently studied sport injuries and can result in serious long-term effects for the athlete.

Shaken Baby Syndrome (SBS) is a serious form of abusive traumatic brain injury, inflicted upon an infant through violent shaking causing rotational head acceleration. Child abuse experts diagnose SBS from two principle symptom findings: subdural hematoma (SDH) and retinal haemorrhage (RH). New research is uncovering alternative causes for both SDH and RH with important medical and legal implications.

A more severe form of TBI is intracranial hematoma. This occurs when an injury to the head causes a blood vessel between the brain and the skull to rupture and the collection of blood compresses brain tissue. Untreated intracranial hematoma can result in serious complications including cerebral ischemia and cerebral infarction.

TBI can also result in more diffuse (as opposed to focal) injuries to the brain such as diffuse axonal injury where strong inertial forces damage the cytoskeleton of myelinated white matter. Subsequently, transport proteins accumulate in axonal swellings, disrupting communication between neurons, ultimately leading to cell death. Unfortunately, diffuse axonal injury is difficult to detect under conventional brain imaging techniques, and often goes undiagnosed. Currently scientists are developing treatments for this injury through either hindering progression of the axonal injury, or through regenerative medicine approaches using embryonic stem cells, neural crest cells, and bone marrow stem cells.

Proper treatment is important to the recovery process following TBI and depending on the nature of the injury, can include physical rehabilitation, surgery, and the use of medication. Erythropoietin (EPO), a peptide hormone endogenously produced in the kidney, is one such treatment. Its principal function is to regulate red blood cell production. However, over the last few decades it has been found to influence many other tissues around the body, brain tissue. Some of the potential benefits including a reduction in inflammation, apoptosis, oxidative damage, and an increase in neurogenesis, as well as the cellular mechanisms and pathways affected by the injury. These pathways have been explored using animal models and a few preliminary clinical trials in humans, which have shown significant results.

1. Concussions in Sports
1. Causes
2. Common Symptoms
3. Long Term Effects
4. Diagnostic Methods
  • 4.1 Mild Concussion
  • 4.2. Moderate Concussion
  • 4.3 Severe Concussion
  • 4.4 Glasgow Coma Scale
5. Diagnostic Imaging
6. Declaring Patient Symptom Free
7. Reasons for the Increase in Occurrences
8. Susceptibility
9. Treatment

2. Shaken Baby Syndrome
1.1 Development of SBS as a diagnosis
1.2 Biomechanical and Animal Studies
2.1 Symptoms of SBS
2.2 SDH mechanism is SBS
2.3 Retinal Hemorrhage
3.1 Medical and Legal Concerns
3.2 Futrue of SBS Diagnosis

3. Intracranial Hematoma
1. Etiology and Classification
2. Clinical Assessment and Diagnosis
  • 2.1 Severity
    • 2.1.1 Glasgow Coma Scale
  • 2.2 Signs and Symptoms
  • 2.3 Imaging Techniques
    • 2.3.1 Traditional Neuro-imaging Techniques
    • 2.3.2 Novel Neuro- Imaging Techniques
3. Treatments
  • 3.1 ICP Monitoring
    • 3.1.1 Craniotomy
    • 3.1.2 Minimally Invasive Surgical Methods
  • 3.2 Anticonvulsant Medications
4. Complications

4. Diffuse Axonal Injury
1.1 Prevalence
2.1 Pathogenesis & Mechanisms
  • 2.1 a. The Biomechanics of DAI
  • 2.1 b. The progression to coma
3.1 Detection and Diagnosis
  • 3.1 a. Neuroimaging Limitations
  • 3.1 b. Prospective Solutions
4.1 Models of DAI
  • 4.1 a. In vitro Animal models and limitations
  • 4.1 b. In vitro Mathematical models of injury
5.1 Therapeutic Approaches
  • 5.1a. Approaches to hinder progression of axonal injury
  • 5.1b. Regenerative Medicine Approaches using stem cells

5. Use of EPO in Treatment of TBI
1 - Animal Models
  • 1.1 Cognition and Motor Function
  • 1.2 Edema
  • 1.3 Lesion Size and Cell Loss
  • 1.4 Neurogenesis
2 - Mechanisms
  • 2.1 Reduced Oxidative Damage
  • 2.2 Anti-Apoptosis
  • 2.3 Blood Brain Barrier Integrity
  • 2.4 EPO and Long-Term Potentiation
  • 2.5 Additional Mechanisms
3 - Human Studies
4 - Additional Considerations

[1] Katz, D. I., & Alexander, M. P. . Traumatic brain injury: Predicting the course of recovery and outcome for patients admitted to rehabilitation. Archives of Neurology, (1994) 51, 661-770.
[2] Corrigan, D., Selassie, W., & Orman, A. The Epidemiology of Traumatic Brain Injury. Journal of Head Trauma Rehabilitation, (2010) 25(3), 224.