Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

Abstract

Acute ischemic and traumatic injury of the central nervous system (CNS) is known to induce a cascade of inflammatory events that lead to secondary tissue damage. In particular, the sterile inflammatory response in stroke has been intensively investigated in the last decade, and numerous experimental studies demonstrated the neuroprotective potential of a targeted modulation of the immune system. Among the investigated immunomodulatory agents, intravenous immunoglobulin (IVIg) stand out due to their beneficial therapeutic potential in experimental stroke as well as several other experimental models of acute brain injuries, which are characterized by a rapidly evolving sterile inflammatory response, e.g., trauma, subarachnoid hemorrhage. IVIg are therapeutic preparations of polyclonal immunoglobulin G, extracted from the plasma of thousands of donors. In clinical practice, IVIg are the treatment of choice for diverse autoimmune diseases and various mechanisms of action have been proposed. Only recently, several experimental studies implicated a therapeutic potential of IVIg even in models of acute CNS injury, and suggested that the immune system as well as neuronal cells can directly be targeted by IVIg. This review gives further insight into the role of secondary inflammation in acute brain injury with an emphasis on stroke and investigates the therapeutic potential of IVIg.

Potential immunotherapies for traumatic brain and spinal cord injury

“…IVIG contains polyclonal IgG and has been extensively used as a first-line therapy with a good pharmacological safety profile in the clinical patients with immunodeficiency and autoimmune diseases such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and Kawasaki disease. 209 , 210 IVIG has been also examined for neuroprotective effects in ischemia-type insults. 210 , 211 , 212 In animal studies, IVIG administration acutely after SCI 213 or TBI 214 significantly improves neural functional recovery.…”

“… 209 , 210 IVIG has been also examined for neuroprotective effects in ischemia-type insults. 210 , 211 , 212 In animal studies, IVIG administration acutely after SCI 213 or TBI 214 significantly improves neural functional recovery. IVIG not only suppresses the excessive immune responses via inhibiting inflammatory cytokine production, immune cell invasion/activation and complement activation in the CNS, but also reverses the concomitant immunosuppression against invading pathogens after CNS injury.…”

Danger signals in stroke and their role on microglia activation after ischemia

“… 56 , 57 Concordantly, the application of anti-IL-17 antibodies reduces infarct sizes and improves neurological outcome. 58 , 59 Prx antibodies can reduce brain damage up to 12 h after ischemia. More than HMGB1, Prxs activate infiltrating macrophages.…”

Aspects of the immune system that impact brain function

“…The development of antibodies specific for undesirable peptides, while most promising in animal models, has not proved as useful in clinical trials as hoped, and has sometimes led to serious undesirable side effects (Wisniewski andGoñi, 2015, Valera et al, 2016). However a less focal approach involving intravenous administration of general immunoglobulins (IVIG) has been more promising and has minimal toxic sequelae (Vitaliti et al, 2017, Thom et al, 2017).…”