Cortexin drug treatment!

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Hello everybody'

In my Turkish parent group, a large number of families followed Cerebrolysin

drug therapy for 2 years.Some of them witnessed big improvement in different

areas of the development in terms of awareness,mostly cognitive and motor skills

etc..I never considered this for my son, I am a cautious person and I hate using

drugs..

Now, they are focusing on Cortexin treatment.When I read some articles, I can

see that it may be effective treatment for important functions of the brain

areas..(You can read as I am copying one of them here)

The families main resources are coming from Russia.Has anyone heard of these two

treatments or are there any members from Russia here?

I also would like to understand why we don'tget this information in the autism

groups,ARI..

At present, some families are neaRrly ready to jump on this treatment, | will

mention this to my neurologist.

Here is one of the article which they shared;

Comparison of Behavioral Effects of Cortexin

and Cerebrolysin Injected into Brain Ventricles

P. D. Shabanov, A. A. Lebedev, V. P. Stetsenko,

N. V. Lavrov, S. V. Markov, and I. V. Vojeikov

Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 143, No.

4, pp. 414-418, April, 2007

Original article submitted October 4, 2006

We compared central effects of polypeptide preparations cortexin and

cerebrolysin

injected into brain ventricles of Wistar rats in doses of 1, 10, and 100

& #956;g. Both drugs

exhibited moderate psychoactivating effect, the effects cortexin were more

pronounced

compared to those of cerebrolysin in all tests.

Key Words: neuropeptides; cortexin; cerebrolysin; central effects; rats

Department of Pharmacology, S. M. Kirov Military Medical Aca

demy, Ministry of Defense of the Russian Federation, St. sburg.

Address for correspondence: shabanov@.... P. D. Sha

banov

Tissue-specific biogenic stimulators are used for

activation of metabolism in organs and tissues,

mainly in those from which they were derived. Preparations

isolated from the brain tissue, cortexin

(CT) and cerebrolysin (CL), attract special attention.

Cortexin is a polypeptide drug isolated from

cattle and porcine brain cortex and created on the

basis of modern pharmaceutical technologies [5,

7,8]. Cortexin is effective in monotherapy and in

combination with traditional methods of treatment.

Cortexin produces tissue-specific, regulatory, and

reparative effects on the brain cortex and contains

active low-molecular-weight neuropeptides (<10 kDa)

penetrating through the blood-brain barrier. The

main tissue-specific characteristic of CT manifests

in neuroprotective, neuromodulating, nootropic,

and anticonvulsant effects [3,4,9]. Cortexin increases

the efficiency of energy metabolism in neurons,

improves intracellular protein synthesis, regulates

neurotransmitter metabolism and lipid peroxidation

processes in the cerebral cortex, optic nerve, and

retinal neurons, stabilizes cerebral bloodflow, prevents

excessive formation of free radicals, and attenuates

neurotoxic effects of stimulatory amino

acids [5,8,9].

The effects of CL (concentrated low-molecularweight

bioactive neuropeptides with a molecular weight

<10 kDa) are similar. Cerebrolysin is characterized

by organ-specific multimodal effect on the brain,

acts as metabolic regulator, functional neuromodulator,

neurotrophic activator, and neuroprotector.

Cerebrolysin is regarded as a nootropic peptidergic

drug with proven neuron-specific neurotrophic activity,

similar to the effects of natural neuron growth

factors, but manifesting, in contrast to latter, under

conditions of peripheral treatment. Cerebrolysin

stimulates the formation of synapses, growth of

dendrites, and prevents activation of microglial cells

and induction of astrogliosis [6,12,13].

We compared the effects of CT and CL in animal

experiments.

MATERIALS AND METHODS

Experiments were carried out on 144 male Wistar

rats (200-220 g), grown in groups of 5 animals.

Males and females were kept separately in standard

plastic cages with free access to water and food

under conditions of inverted light (8.00-20.00) at

22±2oC. All behavioral experiments were carried

out on adult (90-100 days) animals in the fall and

winter

Cortexin (Gerofarm) and CL (Ebewe Pharma)

were infused into the lateral brain ventricle through

an implanted cannula. Guide metal cannulas (200

& #956; in diameter) were implanted into the left ventricle

of the brain unipolarly by coordinates: AP=0.9 mm

behind the bregma, SD=1.4 mm laterally from the

sagittal suture, and H=3.5 mm from the skull surface.

For intraventricular infusion of the test drugs,

metal microcannulas (100- & #956;) with tips 0.2 mm longer

than the guides were inserted into the guides.

The drugs were infused into the brain ventricles in

doses of 1, 10, and 100 & #956;g. The choice of doses

was based on the preferable use of these doses in

behavioral experiments. All substances were infused

5-10 min before the experiment. Infusion of

0.9% NaCl solution served as the control.

Free motor activity of animals was recorded in

the open field test [10,11] (open field was a round

area 80 cm in diameter with 16 holes 3 cm in diameter

each). The duration of 1 experiment was 3

min. Elementary motor acts and postures were registered:

horizontal and vertical activities, grooming,

explored holes, defecation, and urination.

The data were mathematically processed.

Elevated plus-maze consisted of 2 open arms

(50×10 cm) and 2 closed arms (50×10 cm) perpendicular

to each other [10] at a height of 1 m above

the floor. The animal was placed into the center of

the maze. The time spent in open and closed arms,

number and duration of peeping down from the

maze platform and closed arms were recorded by

pressing an appropriate key of the etograph connected

to computer. The duration of the test was

5 min.

Aggressive behavior was studied in the intruder-

resident test [11] in adult rats. A smaller animal

(intruder) was placed into the cage with a large

male (resident). The number of behavioral manifestations

of aggressiveness and defense and total

number of behavioral acts describing the interrelationships

between the animals were registered.

Stereotaxic implantation of electrodes into the

rat brain was carried out under nembutal narcosis

(50 mg/kg) using a stereotaxic device (Medicor).

Monopolar nichrome glass-insulated electrodes (electrode

diameter 0.25 mm, tip length 0.25-0.30 mm,

thickness 0.12 mm) were bilaterally implanted into

the lateral hypothalamic nucleus according to coordinates:

AP=2.5 mm behind the bregma, SD=2.0

mm laterally from the saggittal suture, and H=8.4

mm from the skull surface. An indifferent nichrome

wire electrode was fixed on the skull. All electrodes

were commutated on a plug-and-socket microunit

fixed on the skull with a self-hardened plastic. Behavioral

experiments were started no earlier than

on day 10 postoperation. After all experiments the

location of electrode tips was verified morphologically.

Ten days after implantation of the electrodes

into the brain the rats were trained to press a lever

in the Skinner cell for electrical stimulation of the

brain (rectangular pulses of negative polarity, 1

msec, 100 Hz, 0.4 sec duration, threshold current

values in the " fixed pack " mode). The frequency

and duration of pressing episodes were registered

automatically. The frequency and duration of each

lever pressing were analyzed. The " dissociation "

coefficient [10] was estimated from these data; this

coefficient is a convenient accessory indicator for

evaluating drug effects.

Each group consisted of at least 10-12 animals.

The results were statistically processed using Student's

t test.

RESULTS

Open field test demonstrated a moderate activating

effect of CT, manifesting in increased horizontal

and vertical activity of animals; the maximum CT

dose (100 & #956;g) moderately reduced their emotionality.

No dose-dependent effect of CT was observed

(Table 1). Similar regularities were observed

after CL treatment, but manifestation of the effects

were less pronounced.

In the elevated plus-maze, CT infusion increased

the number of open-arm entries and peeping

down from the platform (Table 2). The maximum

effect was produced by CT in a dose of 1 & #956;g. The

anxiolytic effect sharply decreased with increasing

the dose. Treatment with CL also led to moderate

anxiolytic effect, but, in contrast to CT, it was less

pronounced and increased in a step-wise mode

attaining the maximum in the dose of 100 & #956;g.

Cortexin in doses of 10 and 100 & #956;g caused a

moderate reduction of the communicative activity

in the intruder-resident test (Table 3). Aggressive

manifestations were most frequent after the dose of

1 & #956;g, after which aggressiveness decreased in a

dose-dependent manner. The defense behavior was

similar. The effects of CL in doses of 10 and 100

& #956;g were similar. The only difference was the absence

of aggressiveness increase after CL infusion,

though defense behavior increased 2-fold after the

dose of 1 & #956;g. Hence, the drug effects were to a

certain measure similar. Importantly, CT and CL

stimulated the aggressiveness and defense system,

which attests to their psychoactivating effects.

Infusion of saline into the brain ventricles virtually

did not modify the frequency of the hypothalamus

autostimulation (Fig. 1). Cortexin in doses

TABLE 1. Effects of CT and CL on Rat Behavior in the Open Field Test (M±m)

CT

Number of crossed squares 15.67±2.02 21.33±2.76 23.67±3.06* 20.33±2.63

Rearings 9.00±1.16 12.00±1.56 11.33±1.46 11.00±1.42

Explored holes 10.00±1.33 11.67±1.56 11.67±1.56 11.67±1.56

Grooming 9.67±1.25 11.00±1.42 12.00±1.56 11.00±1.42

Number of defecation boluses 5.83±0.77 4.33±0.57 4.00±0.53 3.33±0.44*

CL

Number of crossed squares 14.33±1.90 17.33±2.30 19.67±2.61* 17.33±2.30

Rearings 10.00±1.29 10.33±1.34 12.00±1.56 10.67±1.38

Explored holes 10.00±1.29 10.00±1.29 11.67±1.51 11.00±1.42

Grooming 9.00±1.19 10.00±1.33 9.67±1.28 10.33±1.37

Number of defecation boluses 4.33±0.56 3.67±0.47 3.33±0.43 2.67±0.34*

Note. Here and in Tables 2 and 3: *p<0.05 compared to the control.

TABLE 2. Effects of CT and CL on Rat Behavior in Elevated Plus-Maze (M±m)

CT

Time in open arms, sec 8.33±1.09 24.33±3.19* 9.00±1.18 14.00±1.84*

Peeping down from central platform

(number of acts) 1.00±0.13 2.67±0.35* 1.67±0.22 1.67±0.22

Peeping out from closed arms

(number of acts) 0.00±0.00 0.00±0.00 0.33±0.04 0.00±0.00

CL

Time in open arms, sec 5.00±0.26 4.00±0.52 9.00±1.18* 17.00±2.23*

Peeping down from central platform

(number of acts) 0.00±0.00 0.00±0.00 1.00±0.13* 2.00±0.26*

Peeping out from closed arms

(number of acts) 0.00±0.00 0.00±0.00 0.00±0.00 0.50±0.07*

of 1 and 10 & #956;g did not change, while in a dose of

100 & #956;g considerably increased the reinforcing effects

of electrical stimulation of the hypothalamus.

Cerebrolysin exhibited less pronounced reinforcing

effect, which was maximum after administration of

10 & #956;g (Fig. 1). Hence, both substances, infused into

brain ventricles exhibited a psychoactivating effect

on the reinforcement systems of the brain.

The maximum stimulation was observed after

administration of 100 & #956;g CT and 10 & #956;g CL. The

absence or slight psychoactivating effects of the

drugs in other doses indicate a typical effect of the

peptide preparations, which, as a rule, work in a

strictly definite range of doses, characteristic of this

or that peptide(s) [1].

The results suggest that CT and CL produce a

moderate psychoactivating effect, the effect of CT

were more pronounced than those of CL. The data

were obtained in experiments with direct infusion

of the drugs into the brain ventricles, that is, avoiding

the blood-brain barrier. This does not rule out

possible differences in the effects of these drugs in

systemic administration.

The mechanism of the action of peptide bioregulator

can be explained from the viewpoint of

the regulatory cascade. They produce a direct information

impact on cell structures of the brain, and

then promote release of the cerebral regulatory peptides,

which in turn, induce the release of the next

group of peptides.

Bulletin of Experimental Biology and Medicine, Vol. 143, No. 4, 2007

PHARMACOLOGY AND TOXICOLOGY

Fig. 1. Effects of CT and CL on rat behavior in the test of autostimulation of

the lateral hypothalamus. a) number of lever pressings over

5 min; dissociation coefficient. Light bars: before drug infusion; dark bars:

after infusion. *p<0.05 compared to values before drug

infusion.

Clinical and biochemical studies demonstrated

a neuromodulating effect of CT on the neurons; it

abolishes (or appreciably reduces) NMDA receptor

blockade, thus preventing further development of

the cascade pathological processes [5]. Used in

therapy of destructive diseases (neuroinfections,

neurotrauma, severe hypoxia), CT supports the damaged

neuron and reduces activity of autoimmune

processes.

The neuroprotective effect of CL manifests in

protection of neurons from the destructive effect of

lactate acidosis, prevention of free radical formation,

and reduction of LPO products concentration

on the ischemia—reperfusion model, improvement

of neuron survival and prevention of their death

under conditions of hypoxia and ischemia, reduction

of the destructive neurotoxic effect of stimulating

amino acids (glutamate), suppression of apoptosis

by caspase inhibition [12,13].

Hence, the main metabolic effects, intrinsic of

the cerebral organ preparations CT and CL, are

neuroprotective with a psychoactivating trend. The

intensity of the drugs effects is different: by the

central effects CT is on the whole superior to CL

under experimental conditions.

The study was supported by the Russian Foundation

for Basic Research (grant No. 04-04-

49672).

REFERENCES

1. I. P. Ashmarin, R. A. Danilova, O. I. Rud'ko, et al., Med. Akad.

Zh., 4, No. 1, 4-13 (2004).

2. P. K. Klimov and G. M. Barashkova, Fiziol. Zh. im. I. M.

Sechenova, 79, 80-87 (1993).

TABLE 3. Effects of CT and CL on Rat Behavior in the Intruder-Resident Test

(M±m)

CT

Individual behavior 39.00±5.07 42.67±5.55 25.00±3.25* 22.33±2.90*

Communicative behavior 38.33±4.98 38.67±5.03 11.33±1.47* 12.00±1.56*

Aggression manifestation 1.67±0.22 3.67±0.48* 0.33±0.04* 0.00±0.00*

Defense behavior 1.67±0.09 5.67±0.74* 1.67±0.22 2.00±0.26

CL

Individual behavior 44.50±5.79 40.67±5.29 26.67±3.47* 24.67±3.21*

Communicative behavior 42.60±5.79 39.67±5.16 22.00±2.86* 25.33±3.29*

Aggression manifestation 0.50±0.07 1.33±0.17 0.00±0.00 0.33±0.04

Defense behavior 2.50±0.33 4.33±0.56* 1.00±0.13 0.33±0.04

P. D. Shabanov, A. A. Lebedev, et al.

3. O. S. Levin and M. M. Sagova, Terra Med., No. 1, 15-19

(2004).

4. S. A. Mikhayevich and N. Yu. Zhivitskaya, Ibid., 42, No. 2,

44-47 (2006).

5. G. A. Ryzhak, V. V. Malinin, and T. N. Platonova, Cortexin

and Regulation of Brain Functions [in Russian], St. sburg

(2003).

6. Vidal Handbook. Drugs in Russia [in Russian], Moscow (2003),

P. B-893.

7. L. S. Chutko, Yu. D. Kropotov, R. G. Yur'yeva, et al., Cortexin

Use in Therapy of the Hyperactivity Attention Disorders Syndrome

in Children and Adolescents. Methodological Recommendations

[in Russian], St. sburg (2003).

8. N. P. Shabalov, A. A. Skoromets, A. P. Shumilina, et al.,

Vestn. Ros. Voen. Med. Akad., 5, No. 1, 24-29 (2001).

9. P. D. Shabanov, V. V. Vostrikov, N. V. Bushkova, et al., Klin.

Patofiziol., No. 1, 66-71 (2006).

10. P. D. Shabanov, A. A. Lebedev, and Sh. K. Meshcherov, Dopamine

and Supporting Systems of the Brain [in Russian], St.

sburg (2002).

11. P. D. Shabanov, V. V. Rusanovskii, and A. A. Lebedev, Zoosocial

Behavior of Mammals [in Russian], St. sburg (2006).

12. E. Schauer, R. Wronski, J. Patockova, et al., J. Neural Transm.,

113, No. 7, 855-868 (2006).

13. G. K. Wong, X. L. Zhu, and W. S. Poon, Acta Neurochir.

Suppl., 95, 59-60 (2005).

I've found short information in PUBMED. also.

nevin