Top Therapies for Immune Modulation in Brain Injuries

Traumatic brain injuries (TBIs) often trigger harmful inflammation that can worsen over time. Managing the immune response is crucial to improving recovery outcomes and reducing long-term damage. This article outlines five key approaches to immune modulation in TBI recovery — four emerging clinical therapies, plus the functional care model offered at HML Functional Care in Lee’s Summit, MO.

• Nasal Anti-CD3 Therapy (Foralumab): Reduces inflammation by activating regulatory T cells (Tregs) that produce IL-10, an anti-inflammatory molecule. Works best within 3 days of injury.
• Erythropoietin (EPO): Reduces inflammation and promotes brain repair. Most effective during the acute phase (6–24 hours post-injury).
• Mesenchymal Stem Cell (MSC) Therapy: Uses stem cells to shift the immune response from harmful to healing. Suitable for subacute to chronic recovery phases.
• Beta-Blocker Treatment (Propranolol): Controls inflammation by blocking stress-related hormones. Administered within 24 hours of injury for best results.
• HML Functional Care: A non-invasive, integrated approach combining functional neurology rehabilitation, neuromodulation, mild hyperbaric oxygen therapy (HBOT), cold laser therapy, and chiropractic care to address the autonomic and neural imbalances common in TBI recovery.

Each therapy has specific timing, mechanisms, and safety considerations, making personalized treatment plans essential for effective recovery.

1. Nasal Anti-CD3 Therapy (Foralumab)

Foralumab is a nasal anti-CD3 therapy that offers a targeted way to manage chronic inflammation in brain injuries. Unlike broad immunosuppressive treatments, it works by promoting regulatory T cells (Tregs) that release interleukin-10 (IL-10), a key anti-inflammatory molecule.

How It Works

When administered nasally, Foralumab stimulates IL-10–producing Tregs. These cells travel from the cervical lymph nodes to the brain, where they interact with microglial cells — the brain’s primary immune defenders. This process reduces inflammation by suppressing pro-inflammatory genes while boosting homeostatic gene expression. The therapy also limits the entry of harmful immune cells, such as neutrophils and monocytes, into the central nervous system.

Treg cells directly reduced chronic microglia inflammation and regulated their phagocytic function in an IL-10-dependent manner. — Nature Neuroscience, 2025

Evidence from Studies

Animal studies have shown promising results in TBI models. When treatment was initiated within 4–6 hours or up to 3 days after injury, researchers observed restored spatial memory (measured by Morris water maze tests), reduced lesion size on MRI, lower levels of brain injury markers (GFAP and UCH-L1), and improvements in motor skills with reduced microgliosis at 30 days post-injury.

Safety Considerations

Foralumab has a favorable safety profile due to its nasal delivery method. The mucosal immune system is naturally designed to promote tolerance, making this approach less toxic compared to systemic immunosuppressive treatments. This makes it a safer option for managing post-TBI inflammation without the risks associated with broader immunosuppression.

Timing Matters

The therapy works best when administered during the acute or early subacute phase — ideally within 4–6 hours or up to 3 days after injury. Starting treatment too late (e.g., 14 days post-injury) has not demonstrated significant behavioral benefits in study models.

2. Erythropoietin (EPO)

Erythropoietin (EPO) is a hormone best known for its role in red blood cell production. However, it also shows meaningful promise in reducing inflammation and cell damage after brain injuries, and its ability to cross the blood–brain barrier makes it particularly relevant in TBI care.

Mechanism of Action

EPO works by binding to its receptor (EPOR), which activates JAK2 and downstream signaling pathways. These pathways help reduce cell death and promote neural stem cell growth while calming the activation of microglia and astrocytes. In brain endothelial cells, EPO lowers pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. It also boosts antioxidant enzyme activity, countering oxidative stress — a major contributor to secondary brain damage.

EPO attenuates inflammation by reducing reactive astrocytosis and microglia activation and by inhibiting immune cell recruitment into the injured area. — Experimental & Translational Stroke Medicine

Clinical Evidence

A meta-analysis of seven randomized trials (1,197 patients) found that EPO improved 6-month survival rates, though results varied by injury type and treatment timing. A 2018 study demonstrated that a high-dose EPO regimen in young rats prevented long-term cognitive and structural brain issues at 90 days post-injury. The largest clinical trial to date, the EPO-TBI study (2010–2015, 603 patients across seven countries), showed an initial survival benefit, though a 6-year follow-up of 356 survivors found that advantage did not persist over time.

Safety Profile

A meta-analysis of 1,197 TBI patients confirmed that EPO does not significantly increase the risk of thromboembolic events, including deep vein thrombosis or pulmonary embolism. Rates of pneumonia, sepsis, seizures, and gastrointestinal issues were comparable between EPO and placebo groups — contrasting with EPO’s use in cancer and chronic kidney disease, where thrombotic risks are higher.

Recovery Phase Applicability

EPO appears most effective when administered during the acute phase, typically within 6 to 24 hours of injury. It shows particular promise where brain trauma is complicated by secondary hypoxia. In animal models, a single dose reduced white matter axonal damage by 60% within 24 hours of combined traumatic axonal injury and hypoxia.

3. Mesenchymal Stem Cell (MSC) Therapy

Mesenchymal stem cells (MSCs), sourced from bone marrow, adipose tissue, or umbilical cord blood, are introduced into the body to help regulate inflammation and promote healing following TBI.

Mechanism of Action

MSCs work by releasing growth factors, exosomes, and proteins (including TSG-6) that suppress the NF-κB pro-inflammatory pathway. This shifts immune cells like microglia and macrophages from a pro-inflammatory state (M1) to a repair-focused state (M2), while lowering inflammatory cytokines such as IL-1β, TNF-α, and IL-6 and increasing anti-inflammatory signals like IL-10 and TGF-β1. MSCs can also “home in” on damaged brain tissue by responding to chemokines and growth factors released at the injury site.

Clinical Evidence

Clinical studies have produced encouraging results. A study of 97 patients found that 39.2% showed improved neurological outcomes within two weeks of receiving autologous bone marrow-derived MSCs. In a pediatric study, 70% of 10 participants showed positive clinical outcomes 6 months after intravenous treatment. A 2024 trial using umbilical cord-derived MSCs (4 infusions via lumbar puncture in 20 TBI patients) showed notable improvements in motor skills, balance, sensation, and social cognition at 6 months compared to controls.

The therapeutic benefits of MSC stem cell infusions for the treatment of TBIs generated significant beneficial results over a relatively wide window of treatment times. — International Journal of Molecular Sciences

Safety Profile

MSCs are generally considered safe, with a low risk of serious adverse events. Some concerns exist around potential cell trapping in the lungs during intravenous delivery and risks tied to repeated dosing. Between 2006 and 2025, approximately 13 clinical trials focused on MSC-based therapies for TBI, most of them early-phase.

Recovery Phase Applicability

MSCs can be effective when administered anywhere from 24 hours to one year after injury. Early treatment (within 3 days) is particularly effective in reducing M1 microglia activation, while delayed administration (up to 14 days) has also demonstrated anti-inflammatory effects and memory improvement. Pairing MSC therapy with rehabilitative treatments has been shown to enhance neural plasticity and functional recovery.

4. Beta-Blocker Treatment (Propranolol)

Propranolol addresses the surge in sympathetic nervous system activity that commonly follows TBI — a state sometimes called a “sympathetic storm” — which drives damaging neuroinflammation if left unchecked.

Mechanism of Action

Propranolol works by blocking beta-adrenergic receptors throughout the brain and body. This tempers the release of pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6, which are typically elevated after TBI. It also crosses the blood–brain barrier, reducing the brain’s oxygen and glucose demands and shielding neurons from damage caused by excess catecholamines. Early use has been shown to lower serum levels of Neuron-Specific Enolase (NSE) and S100B — both markers of ongoing brain cell damage.

Clinical Evidence

The BBTBBT trial (350 patients, Hamad Level I Trauma Centre, Qatar, 2021–2023) demonstrated that early propranolol use significantly reduced IL-6, IL-1β, and epinephrine levels within 48 hours. A study at Shiraz University Hospital (154 patients with isolated severe TBI) found a mortality rate of just 4.4% in the propranolol group vs. 18.6% in the control group, with patients on propranolol also 20% more likely to achieve favorable functional outcomes at 6 months. A broader meta-analysis reported an odds ratio of 0.33 for in-hospital mortality among TBI patients treated with beta-blockers.

Propranolol decreases in-hospital mortality and improves long-term functional outcome in isolated severe TBI. This randomized trial speaks in favor of routine administration of beta-blocker therapy as part of a standardized neurointensive care protocol. — World Journal of Surgery

Safety Profile

Propranolol is generally well-tolerated under proper supervision. In clinical trials, approximately 27% of patients experienced temporary bradycardia, and 2% had manageable episodes of hypotension. The drug is contraindicated in patients with persistent shock, systolic blood pressure below 100 mmHg, heart rate under 60 bpm, or severe asthma. Glucose levels should be monitored closely in diabetic patients.

Recovery Phase Applicability

Propranolol is typically initiated within 24 hours of injury (provided the patient’s systolic BP is above 100 mmHg and vasopressor support is no longer required) and continued for 6 to 10 days or until discharge. Heart rate and blood pressure should be monitored closely during the first 24 hours, with doses adjusted to achieve a 10–20% heart rate reduction.

5. HML Functional Care: Integrated Neurological Rehabilitation for TBI

While the therapies above address the acute immune response, recovery from TBI doesn’t end when the critical phase is over. The subacute and chronic stages of recovery — where most patients live day-to-day — require a different kind of care: one that addresses the ongoing neurological imbalances, lingering autonomic dysregulation, and functional deficits that pharmaceuticals alone cannot fully resolve.

HML Functional Care in Lee’s Summit, MO, bridges that gap. Led by Drs. Alex and Lauren Nelson, the clinic combines advanced functional neurology, chiropractic care, and functional medicine to support TBI recovery from the subacute phase through long-term rehabilitation.

How HML Addresses the Neural-Immune Connection

TBI frequently triggers what is known as a “sympathetic storm” — an overactivation of the autonomic nervous system driven by elevated catecholamines. This sustained stress response perpetuates neuroinflammation and impairs the brain’s ability to heal. HML’s approach directly targets this dysregulation through neuromodulation and nervous system rehabilitation, working to restore autonomic balance and support the brain’s natural recovery processes.

This makes HML’s care a natural complement to acute-phase therapies like propranolol and EPO, where those therapies reduce the initial inflammatory surge, HML’s approach helps retrain and stabilize the nervous system in the weeks and months that follow.

Treatments Offered at HML Relevant to TBI Recovery

Functional Neurology Rehabilitation: HML’s core offering. Using targeted neurological exercises, coordination training, and repetition-based rehabilitation, the Nelsons work to restore neural pathways disrupted by injury. This includes brain hemispheric integration — using sensory input (sight, sound, smell, tactile stimulation, and proprioception) to balance activity between the left and right hemispheres of the brain.

Mild Hyperbaric Oxygen Therapy (HBOT): Patients breathe concentrated oxygen inside a pressurized chamber, which allows oxygen to dissolve more readily into the blood and reach areas of the brain that may have restricted circulation post-injury. HBOT directly addresses one of the core mechanisms of secondary brain damage — hypoxia — reducing inflammation and supporting cellular healing. It is one of the most clinically relevant non-pharmaceutical tools available for TBI recovery. Learn more about HBOT at HML →

Cold Laser Therapy / Photobiomodulation (PBM): Cold laser light penetrates tissues and energizes cells by increasing oxygenation, stimulating energy production (ATP), reducing inflammation, and accelerating waste elimination. Applied over the head and cervical spine, PBM is emerging as a promising non-invasive tool for neurological inflammation reduction and tissue repair — directly relevant to TBI recovery. Learn more about Cold Laser at HML →

Interactive Metronome: Brain function requires precise timing, rhythm, and coordination of neurons. The Interactive Metronome challenges patients to synchronize whole-body movements to a millisecond-level beat, providing auditory and visual feedback that retrains the brain’s timing and processing networks — areas commonly disrupted by TBI.

Neurosage: A form of carefully applied neural stimulus that uses Systemic Neural Adaptation to help unlock the brain’s capacity to heal, reduce pain, and improve cognitive and physical performance. Particularly useful for patients managing chronic post-TBI symptoms.

RightEye & Senaptec: Advanced eye-tracking and sensory evaluation tools that allow HML to assess functional vision, brain health, and sensory processing deficits — all of which are commonly impacted by TBI. These tools guide targeted rehabilitation and track measurable recovery progress.

Functional Medicine: HML addresses the biochemical side of TBI recovery through functional medicine, including food sensitivity testing (Array 10 and Array 10-90), nutritional support, and identifying underlying factors that may be prolonging inflammation or slowing healing.

Chiropractic Care: Spinal adjustments restore mobility and reduce mechanical stress on the nervous system, which is frequently compromised in TBI patients who have suffered whiplash or other cervical trauma alongside their brain injury. Explore HML’s full treatment menu →

Who HML Serves

HML specializes in adults and children with neurological conditions, including post-concussion syndrome, traumatic brain injury, stroke rehabilitation, movement disorders, ADHD, autism, and vertigo/dizziness. Patients who have “hit a ceiling” with conventional medicine and are looking for integrative, science-backed care find HML’s model particularly effective.

Learn more about HML’s TBI practice area:  HML Traumatic Brain Injury page →

Therapy Comparison Table

The table below provides a side-by-side overview of the five approaches covered in this article, comparing mechanism, evidence, safety, and optimal recovery timing.

Timing is a critical variable in TBI immune modulation. Acute-phase therapies — EPO, Propranolol, and Nasal Anti-CD3 — must be administered within hours to days of injury. HML Functional Care and MSC Therapy are better suited to the subacute-to-chronic phase, where ongoing neurological rehabilitation and systemic support are most impactful.

Conclusion

TBI affects an estimated 50 million people globally each year, and its long-term consequences — from chronic neuroinflammation to cognitive and functional decline — remain inadequately addressed by a single treatment approach. The therapies reviewed here represent the current landscape of immune modulation in TBI, each targeting the neural-immune balance at different stages and through different mechanisms.

Recovery outcomes depend heavily on timely, personalized intervention. Acute-phase therapies like EPO, propranolol, and nasal anti-CD3 can dramatically alter the early inflammatory trajectory. In the weeks and months that follow, integrated functional care — including HBOT, cold laser therapy, functional neurology rehabilitation, and chiropractic care — can support the brain’s continued healing and help patients rebuild functional capacity.

Many of these pharmaceutical therapies remain experimental or are not yet FDA-approved as disease-modifying TBI treatments. Functional neurology and integrative care, by contrast, are available now and carry strong safety profiles. As always, care should be guided by qualified healthcare providers familiar with both the neuroscience and the individual patient.

HML Functional Care’s integrated model is built precisely for this — meeting patients where they are in recovery and equipping them with tools that go beyond symptom management toward lasting restoration.

Frequently Asked Questions

Which immune therapy fits my TBI recovery stage?

The best approach depends on your stage of recovery and how your immune system is responding. In the first hours and days post-injury, pharmaceutical interventions like EPO, propranolol, and nasal anti-CD3 may be applicable under hospital-based care. As you transition out of the acute phase, integrative functional care — like that offered at HML — becomes central to restoring neurological function and addressing the root causes of ongoing symptoms. Work with a provider who specializes in neuroimmunology or neurorehabilitation to determine the right plan for your situation.

Can these therapies be combined safely?

Yes, in many cases these approaches are complementary rather than competing. The pharmaceutical therapies are administered in acute hospital settings, while HML’s functional care model is designed for the outpatient, subacute-to-chronic phase. Combining stem cell therapy with rehabilitative care is also being actively studied. Any combination of treatments should be managed by and coordinated between qualified healthcare providers.

Are these treatments FDA-approved for TBI?

There are currently no FDA-approved disease-modifying treatments specifically for traumatic brain injury. Some therapies reviewed here — such as nasal foralumab — have received FDA approval for other neurological conditions (e.g., multiple system atrophy) and are being studied for TBI under research protocols. HML’s functional neurology and chiropractic care, HBOT, and cold laser therapy are established clinical practices with strong safety profiles and are available to patients now. Always consult qualified healthcare providers before beginning any treatment regimen.